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1.
Article in Chinese | WPRIM | ID: wpr-1018270

ABSTRACT

Objective:To investigate the protective effects and mechanism of Shenyan 1 Prescription on renal fibrosis of unilateral ureteral obstruction (UUO) rats through TGF- β 1/Smad homologous 3 (Smad3) pathway regulating ferroptosis.Methods:Totally 48 male SD rats were divided into four groups: sham-operation group, UUO model group, and Shenyan 1 Prescription low-(10 drug/kg) , and high-dosage (20 crude drug/kg) groups according to random number table method, with 12 rats in each group. The UUO model was induced by the method of unilateral ureteral obstruction except for those sham-operation group. After modeling, rats received corresponding drugs or normal saline by gavage for 4 weeks, once per day. After 4 weeks, the body mass and the left kidney weight were measured. The 24 h urine protein and the levels of serum albumin (ALB), alanine aminotransferase (ALT), serum creatinine (SCr) and blood urea nitrogen (BUN) were detected by biochemical analysis method; the ROS level in renal tissue was measured using a chemical fluorescence assay kit, and the SOD and MDA levels in left renal tissue of rats were measured using ELISA method; the morphology of renal tissue and the specific blue staining of hemosiderin were observed using HE and Prussian blue staining methods, respectively; the expressions of transforming growth factor-β1 (TGF-β1), Smad3, glutathione peroxidase 4 (GPX4), and solute carrier family 1 member 5 (SLC1A5) were detected by Western blot.Results:Compared with the model group, the 24 h urinary protein excretion in Shenyan 1 Prescription high-dosage group decreased ( P<0.05), the serum ALB level increased ( P<0.05), the ALT level decreased ( P<0.05), and the expression of SLC1A5 in renal tissue decreased ( P<0.05); the left kidney weight/body decreased in Shenyan 1 Prescription low- and high-dosage groups ( P<0.05); the levels of serum ROS and MDA decreased ( P<0.05), and the activity of SOD significantly increased ( P<0.05); the expressions of TGF-β1 and Smad3 in renal tissue decreased ( P<0.05), and the expression of GPX4 increased ( P<0.05), and the renal pathological injury and ion deposition were improved. Conclusion:Shenyan 1 Prescription has a protective effect on the structure and function of renal tissues in UUO rats through regulating ferroptosis via inhibition of the TGF-β1/ Smad3 pathway to inhibit renal fibrosis of UUO rats.

2.
Tianjin Medical Journal ; (12): 50-55, 2024.
Article in Chinese | WPRIM | ID: wpr-1020969

ABSTRACT

Objective To explore the effect and mechanism of anti-mesangial cell-proliferation-peptide 2(AMPP2)on mesangial cell proliferation induced by transforming growth factor β1(TGF-β1).Methods Mesangial cells were cultured in vitro and treated with TGF-β1(10 μg/L)and AMPP2(10 ng/L).According to different intervention factors,mesangial cells were divided into four groups:the control group,the AMPP2 group,the TGF-β1 group and the TGF-β1+AMPP2 group.The proliferation activity of mesangial cells was detected by CCK-8.The relative protein expression of cyclin dependent kinase 4(CDK-4),cyclin dependent kinase 6(CDK-6),proliferating cell nuclear antigen(PCNA),α-smooth muscle actin(α-SMA),collagen-Ⅰ(COL-Ⅰ)and fibronectin(FN)were examined by Western blot assay.The relative mRNA expression of α-SMA,COL-Ⅰ and FN were detected by qPCR.Results Compared with the control group,proliferation activity of mesangial cells was significantly increased in the TGF-β1 group(P<0.05).The proliferation activity of mesangial cells was markedly decreased in the TGF-β1+AMPP2 group compared with that of the TGF-β1 group(P<0.05).Compared with the control group,protein levels of CDK-4,CDK-6,PCNA,α-SMA,COL-Ⅰand FN in cells were significantly increased in the TGF-β1 group(P<0.05),as well as the mRNA levels of α-SMA,COL-Ⅰand FN(P<0.05).In the TGF-β1+AMPP2 group,the protein and mRNA levels of α-SMA,COL-Ⅰand FN and the protein levels of CDK-4,CDK-6 and PCNA were markedly decreased compared with those of the TGF-β1 group(P<0.05).Compared with the control group,levels of p-SMAD3/SMAD3 was remarkably upregulated in the TGF-β1 group(P<0.05),while levels of p-SMAD3/SMAD3 was remarkably downregulated in the TGF-β1+AMPP2 group compared with those of the TGF-β1 group(P<0.05).Conclusion AMPP2 may inhibit mesangial cell proliferation by regulating TGF-β1/SMAD3 pathway.

3.
Article in Chinese | WPRIM | ID: wpr-989607

ABSTRACT

Objective:To investigate the protective effect and possible mechanism of Tangshenbao on renal damage in diabetic nephropathy (DN) rats.Methods:Totally 36 SPF male SD rats were randomly divided into normal group ( n=6) and model group ( n=30). The DN rat model was prepared by single high-dose intraperitoneal injection of STZ. According to the random number table method, the rats were divided into model group, irbesartan group and Tangshenbao low-, medium- and high-dosage groups, with 6 rats in each group. Drug intervention lasted for 8 weeks. The general condition and body weight of rats in each group were recorded. The blood glucose, kidney index, 24 h urine protein (24 h UTP), SCr and BUN levels were detected. The pathological morphology of renal tissue was observed by PAS staining and transmission electron microscopy. The mRNA and protein expressions of Ets-1, TGF-β1, Smad2 and Smad3 in renal tissue were detected by real-time fluorescence quantitative PCR and Western blot. Results:Compared with model group, the body weight of Tangshenbao low, medium and high dose groups and irbesartan group significantly increased ( P<0.01). The kidney index decreased ( P<0.05 or P<0.01). The contents of 24 hUTP, BUN and SCr significantly decreased ( P<0.05 or P<0.01). Glomerular volume was significantly reduced ( P<0.05 or P<0.01), the mRNA expressions of Ets-1 (1.59 ± 0.06, 1.47 ± 0.04, 1.31 ± 0.03, 1.39 ± 0.03 vs. 1.64 ± 0.04), TGF-β1 (1.65 ± 0.05, 1.59 ± 0.03, 1.38 ± 0.05, 1.49 ± 0.04 vs. 1.77 ± 0.08), Smad2 (1.48 ± 0.05,1.39 ± 0.05, 1.22 ± 0.03, 1.31 ± 0.04 vs. 1.54 ± 0.05), Smad3 (1.57 ± 0.04, 1.48 ± 0.03, 1.28 ± 0.03, 1.39 ± 0.02 vs. 1.64 ± 0.05) in renal tissue of rats significantly decreased ( P<0.05 or P<0.01), the protein expressions of Ets-1 (1.33 ± 0.32, 1.16 ± 0.38, 0.77 ± 0.06, 0.84 ± 0.06 vs. 1.97 ± 0.43), TGF-β1 ( 1.35 ± 0.14, 1.24 ± 0.22, 0.94 ± 0.13, 1.07 ± 0.06 vs. 1.63 ± 0.20), Smad2 (1.24 ± 0.26, 1.14 ± 0.31, 0.77 ± 0.28, 0.85 ± 0.19 vs. 1.72 ± 0.34) and Smad3 (1.29 ± 0.14, 1.19 ± 0.21, 0.85 ± 0.39, 0.90 ± 0.37 vs. 1.76 ± 0.21) decreased ( P<0.05 or P<0.01). Conclusion:Tangshenbao can improve renal damage in DN rats, and its mechanism may be related to the inhibition of Ets-1 expression and TGF-β1/Smads signaling pathway.

4.
Article in Chinese | WPRIM | ID: wpr-989628

ABSTRACT

Objective:To investigate the effects of alum ice nanoemulsion on VEGF and TGF-β1 in hypertrophic scar based on Notch signaling pathway.Methods:Totally 144 SD rats were divided into blank control group, model group, triamcinolone acetonide group and alum ice nanoemulsion low-, medium- and high-dose groups according to random number table method, with 24 rats in each group. Except for the blank control group, the rats in other groups were prepared with deep Ⅱ ° burn models. 24 hours after the successful modeling, the model group was given the same amount of normal saline, the rats in alum ice nanoemulsion low-, medium- and high-dose groups were given 8.15, 6.30 and 32.60 mg/ml alum ice nanoemulsion respectively, and the triamcinolone acetonide group was given triamcinolone acetonide twice a day, 0.2 ml each time, for 35 consecutive days. At 14, 21, 28 and 35 d, the collagen fiber surface density was calculated by VG staining. The protein expressions of vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), Notch1 and Jagged1 were detected by Western Blot. The expressions of Notch1 mRNA and Jagged1 mRNA were detected by RT-PCR.Results:Compared with model group, triamcinolone acetonide and different doses of alum ice nanoemulsion groups could decrease collagen fiber surface density, protein expressions of VEGF, TGF-β1, Notch1, Jagged1 and mRNA expressions of Notch1, Jagged1 in different degrees ( P<0.05). Compared with the triamcinolone acetonide group, the collagen fiber surface density, protein expressions of VEGF, TGF-β1, Notch1 and Jagged1 and mRNA expressions of Notch1, Jagged1 in the alum ice nanoemulsion medium-dosage group decreased ( P<0.05). Conclusion:Alum ice nanoemulsion can inhibit hypertrophic scar formation, and its mechanism is related to down-regulating Notch signal pathway related molecules Notch1, Jagged1 protein and mRNA levels, and then down-regulating VEGF and TGF-β1 protein expressions.

5.
J Vector Borne Dis ; 2022 Apr; 59(2): 163-171
Article | IMSEAR | ID: sea-216877

ABSTRACT

Background & objectives: In this study, we aimed to investigate the relationship between serum TGF-?1 and PDGFB levels with the pathogenesis, clinical course and prognosis of adult Crimean-Congo hemorrhagic fever (CCHF) patients. Methods: 50 adult patients and 30 healthy individuals as a control group were included in the study, who were followed up and treated with the diagnosis of CCHF at the Atatürk University Faculty of Medicine Infectious Diseases and Clinical Microbiology Clinic, between March 2017 and September 2019 in Eastern Anatolia Region in Turkey. Blood samples were taken from patients on the first day of their hospitalization and on the sixth day of their complaints. TGF-?1 and serum PDGF-B levels were studied by ELISA method using commercial kits, from serum samples taken from CCHF patient group and individuals in healthy control group and stored at -80°C. Results: While the serum TGF- ?1 levels of patients with CCHF were found to be significantly higher on the sixth day of their complaints compared to the first day of hospitalization (42.33 ± 15.42, 28.40 ± 7.06, p = 0.001, respectively), the serum PGDF-B levels were found to be significantly lower on the sixth day of their complaints compared to those measured on the day of hospitalization (62.14 ± 19.75, 93.96 ± 20.02, respectively, p = 0.001). Interpretation & conclusion: Serum TGF-?1 levels are higher and PDGF-B levels are lower in CCHF patients with severe disease, indicating that serum TGF-?1 and PDGF-B play an important role in the pathogenesis of CCHF

6.
Article in Chinese | WPRIM | ID: wpr-930141

ABSTRACT

Objective:To observe the effect of Ginsenoside Re on the proliferation and protein secretion of primary cardiac fibroblasts (CFs) cultured in high glucose by vitro, and the regulation of Wnt/β-catenin signaling pathway.Methods:The myocardial fibroblast proliferation model induced by high glucose in vitro was used. Cell proliferation was detected by MTT method, cell cycle was measured by flow cytometry, concentration of type Ⅰ,Ⅲ collagens and TGF-β 1 protein were tested by ELISA assay. Protein expression of β-catenin, GSK-3β and p-GSK-3β were determined by Western blot. Results:Compared with the model group, the cell proliferation in Ginsenoside Re high, medium, low group were significantly decreased ( P<0.01), the percentage of cells in G 0 + G 1 phase was increased ( P<0.01), and the percentage of cells in S + G 2 + M phase was decreased ( P<0.01), the content of TGF-β 1 was significantly decreased( P<0.01). The content of type Ⅲ collagen [(6.566±1.620)ng/ml,(7.170±0.470)ng/ml vs. (11.241±2.234)ng/ml] in Ginsenoside Re high, medium group were significantly decreased ( P<0.01). The expression of β-catenin (0.281±0.016, 0.301±0.021 vs. 0.409±0.037) was significantly decreased and the expression of p-GSK-3β (0.369±0.049 vs. 0.268±0.048) in Ginsenoside Re high, medium group were significantly increased ( P<0.01). Conclusion:Ginsenoside Re plays an important role in inhibiting CFs proliferation and reducting the synthesis of collagen and TGF-β 1 by regulating abnormal expression of Wnt/β-catenin signaling pathway. It has the potential to delay the myocardial fibrosis of diabetes mellitus.

7.
Article in Chinese | WPRIM | ID: wpr-931702

ABSTRACT

Objective:To investigate the effects of tamoxifen on high glucose-induced epithelial-to-mesenchymal transition of rat peritoneal mesothelial cells and the underlying mechanism.Methods:The peritoneal mesothelial cells of normal male SD rats were selected between January 2015 and June 2016 and then cultured and divided into blank control, high-glucose stimulation and drug intervention groups. High-glucose stimulation group: primary cultured rat peritoneal mesothelial cells (RPMCs) were treated with 60 mmol/L high-concentration glucose to induce epithelial-to-mesenchymal transition. Drug intervention group: (1) RPMCs were treated with 60 mmol/L high-concentration glucose and different concentrations (0.5 μmol/L, 2 μmol/L) of tamoxifen. After 72 hours of stimulation, protein was extracted. (2) RPMCs were treated with 60 mmol/L high-concentration glucose and 2 μmol/L tamoxifen with or without 2 μmol/L ER-α antagonist for 1 hour to extract protein and for 6 hours to extract RNA. (3) RPMCs were treated with high-concentration glucose and 2 μmol/L tamoxifen with or without 1 μmol/L 1 μM proteasome inhibitor for 1 hour to extract protein. Western blot analysis was performed to analyze change in E-cadherin, α-SMA, Smad2, p-Smad2, Smad3, p-Smad3 and Smad4 protein. Real-time fluorescence quantitative PCR was performed to detect the change in mRNA expression of Smad2, Smad3, connective tissue growth factor and plasminogen activator inhibitor 1.Results:Tamoxifen attenuated epithelial-to-mesenchymal transition on RPMCs induced by high-level glucose, showing increased expression of epithelial cell marker E-cadherin and decreased expression of α-SMA in a concentration-dependent manner ( tE-cadherin = 2.31, tα-SMA =-2.53, both P < 0.05).TGF-β1/R-Smad signal pathway was activated by high-concentration glucose. Phosphorylation of Smad2/3 and mRNA expression of CTGF and PAI-1 were increased. Tamoxifen remarkably reduced protein and mRNA level of above mentioned protein and related target genes ( tp-Smad2 = -3.38, tCTGF = -3.81, P < 0.05), which could be blocked by ER-α antagonist. Finally, proteasome inhibitor could weaken the inhibitory effects of tamoxifen on p-Smad2/3 and increase p-Smad2/3 protein level ( tp-Smad2 = 3.94, P < 0.05). Conclusion:Tamoxifen activates ER-α on RPMCs, weakens the activation of TGF-β1/R-Smad signal pathway through decreasing p-Smad2 protein level, and effectively inhibits the progression of high-concentration glucose-induced epithelial-to-mesenchymal transition possibly through degrading p-Smad2 protein through proteasome. The role of tamoxifen in epithelial-to-mesenchymal transition may provide a possible guide for research, prevention and treatment of peritoneal fibrosis.

8.
Clinical Medicine of China ; (12): 268-273, 2022.
Article in Chinese | WPRIM | ID: wpr-932179

ABSTRACT

Objective:To investigate the correlation between serum concentration of vasohibin-1 (VASH-1) and urinary albumin creatinine ratio (UACR) in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy.Methods:The clinical data of 196 patients with T2DM from February 2017 to December 2020 were analyzed retrospectively. According to whether diabetic nephropathy (DN) was combined, 33 patients without DN of T2DM were divided into the control group,and 163 patients with DN of T2DM were divided into the case group, and the case group was divided into four groups:normal albuminuria group (groupⅠ, UACR <30 mg/g, 21 cases),microalbuminuria group (groupⅡ, UACR ≥30-≤300 mg/g, 50 cases), clinical albuminuria group (group Ⅲ, UACR>300 mg/g, 43 cases), and clinical albuminuria hypertensive group (groupⅣ, UACR >300 mg/g with hypertension, 49 cases). Serum levels of VASH-1,C-reactive protein(CRP), erythrocyte sedimentation rate (ESR) and transforming growth factor β1 (TGF-β1) with other biochemical indicators were measured. T-test was used for comparison between measurement data groups in accordance with normal distribution, one-way ANOVA was used for comparison between multiple groups, q-test was used for pairwise comparison, and χ2 test was used for comparison between counting data groups. The influencing factors were analyzed by multivariate Logistic regression.Pearson correlation analysis was used to analyze the correlation between vash-1 and UACR. Results:UACR((1 175.9±120.4) mg/g), CRP((9.80±2.01) mg/L), ESR((20.61±2.20) mm/h),TGF-β1((16.75±2.05) μg/L), VASH-1((645.3±183.5) ng/L) in case group were higher than that in the control group((11.5±2.0) mg/g, (4.77±1.34) mg/L, (8.33±1.56) mm/h, (10.63±1.97) μg/L, (416.3±162.1) ng/L), and there were significant differences between the two groups ( t=123.39,13.76,30.54,15.75,6.66; all P<0.001). Multivariate logistic regression analysis showed that VASH-1 ( OR=1.881,95% CI 1.146-3.089), UACR( OR=1.511,95% CI 1.064-2.146), TGF-β1( OR=1.846,95% CI 1.135-3.001)were all risk factors for DN of T2DM ( P values were 0.009, 0.022 and 0.012). Serum VASH-1 ((693.5±201.4), (709.8±214.7) ng/L] in group Ⅲ and group Ⅳ were higher than those in group Ⅰ and group Ⅱ ((585.3±162.1), (632.9±165.5) ng/L). There was significant difference between the two groups ( F=129.46, P<0.001). The CRP ((7.08±1.36), (8.99±3.72), (10.58±3.48), (11.64±3.50) mg/L), ESR ((17.36±1.76), (19.05±4.12), (21.45±5.74), (22.69±9.13) mm/h) and TGF- β1 ((14.75±1.97), (16.50±1.90), (17.06±1.23), (18.39±1.46) μg/L) of groupⅠ, groupⅡ, groupⅢ and groupⅣ increased gradually, and there were significant differences between the four groups ( F values were 73.48, 156.61, 25.83; all P<0.001). Pearson correlation analysis showed that there was a significant positive correlation between VASH-1 and UACR ( r=0.532, P=0.008). Conclusion:The concentration of VASH-1 in serum of patients with T2DM complicated with DN increased with the increase of UACR. VASH-1 may become a new marker for predicting early DN of T2DM.

9.
Article in Chinese | WPRIM | ID: wpr-934584

ABSTRACT

Objective: To observe the effect of moxibustion on the colonic mucosal barrier of rats with ulcerative colitis (UC) induced by dextran sulfate sodium (DSS). Methods: Forty male Sprague-Dawley rats were randomly divided into a normal group and a modeling group, with 20 rats in each group. Rats in the modeling group were subjected to preparing experimental UC models by drinking 4% DSS for seven consecutive days. Two modeled rats and two normal rats were randomly selected for model identification. After the success of UC model was confirmed, the remaining 18 modeled rats were randomly divided into three groups, a model group, a model + herbal cake-partitioned moxibustion group, and a model + mild moxibustion group, with six rats in each group; the remaining normal rats were randomly divided into three groups, a normal group, a normal + herbal cake-partitioned moxibustion group, and a normal + mild moxibustion group, with six rats in each group. After 7 d of intervention with the herbal cake-partitioned moxibustion or the mild moxibustion, hematoxylin-eosin (HE) staining technique was used to observe the pathological changes of colon tissue under a light microscope; Western blotting and/or immunohistochemical techniques were used to detect the protein expression levels of Occludin, Claudin, junction adhesion molecular 1 (JAM1), mucin 2 (MUC2), and transforming growth factor beta1 (TGF-β1) in rat colon tissue. Results: Compared with the normal group, the colon tissue was severely damaged, the pathological score was significantly increased, and the protein expression levels of Occludin, Claudin, JAM1, MUC2, and TGF-β1 were significantly decreased in the model group (P<0.01); while there were no significant differences in the colonic histopathological score, protein expression levels of Occludin, Claudin, JAM1, MUC2, and TGF-β1 in the normal + herbal cake-partitioned moxibustion group and the normal + mild moxibustion group (P>0.05). Compared with the model group, the model + herbal cake-partitioned moxibustion group and the model + mild moxibustion group showed repaired colon tissue, ulcer healing, significantly reduced pathological score, and significantly increased protein expression levels of JAM1, MUC2, and TGF-β1 (P<0.05); the Occludin protein expression level in the colon tissue of the model + mild moxibustion group was increased (P<0.01). Conclusion: Neither herbal cake-partitioned moxibustion nor mild moxibustion influences the colonic histopathology and intestinal mucosal barrier-related protein expression in the normal rats; both herbal cake-partitioned moxibustion and mild moxibustion can up-regulate the protein expression levels of JAM1, MUC2, and TGF-β1 in the colon tissue of UC rats. Mild moxibustion can up-regulate Occludin protein expression. This may be a mechanism of moxibustion in reducing colonic mucosa inflammation in UC.

10.
Article in Chinese | WPRIM | ID: wpr-958862

ABSTRACT

Objective: To observe the efficacy of mild moxibustion combined with arthroscopic meniscal repair in the treatment of meniscal injury and to explore its action mechanism. Methods: Ninety-eight patients with meniscal injury were divided into a surgery group and a moxibustion plus surgery group by the random number table method, with 49 cases in each group. Both groups received arthroscopic meniscal repair, and the moxibustion plus surgery group was treated with add-on mild moxibustion. The Lysholm score, visual analog scale (VAS) score, and mobility of the affected knee were measured before and after treatment, and transforming growth factor (TGF)-β1 and platelet-derived growth factor (PDGF) levels were measured in the fluid of the affected knee joint. The healing of the meniscus was recorded at a follow-up visit 3 months after the surgery. Results: After treatment, the Lysholm score increased, the VAS score decreased in both groups, and the intra-group differences in both groups were statistically significant (P<0.05). The Lysholm score was higher in the moxibustion plus surgery group than in the surgery group, and the VAS score was lower in the moxibustion plus surgery group than in the surgery group. The differences between groups in both scores were statistically significant (P<0.05). The mobility of the affected knee joint increased in both groups (P<0.05), and it was greater in the moxibustion plus surgery group than in the surgery group (P<0.05). When compared with pretreatment, the levels of TGF-β1 and PDGF in the fluid of the knee joint increased in both groups (P<0.05), and the levels of TGF-β1 and PDGF in the fluid of the affected knee joint were higher in the moxibustion plus surgery group than in the surgery group (P<0.05). The healing of the meniscus in the moxibustion plus surgery group was significantly better than that in the surgery group at the follow-up visit 3 months after the surgery (P<0.05). Conclusion: The effect of mild moxibustion combined with arthroscopic meniscal repair is better than the surgery alone in improving knee function, relieving pain, increasing mobility of the affected knee, and promoting meniscal healing, which may be related to the up-regulation of TGF-β1 and PDGF levels in the fluid of knee joint.

11.
Journal of Clinical Hepatology ; (12): 2040-2045, 2022.
Article in Chinese | WPRIM | ID: wpr-942657

ABSTRACT

Objective To investigate the effect of Yangxue Rougan pills on a rat model of liver fibrosis induced by multiple factors and the mechanism of action of Yangxue Rougan pills in the treatment of liver fibrosis. Methods A total of 50 male rats were randomly divided into blank control group, multi-factor model group, Fuzheng Huayu capsule group, and high-, middle-, and low-dose Yangxue Rougan pill groups. The rats in the blank control group were given normal water and feed, and those in the other groups were given modified high-fat low-protein diet and 5% alcohol, as well as subcutaneous injection of olive oil solution containing 40% carbon tetrachloride and intraperitoneal injection of pig serum 0.5 mL per rat, twice a week for 12 consecutive weeks. Since week 7, the rats in the high-, middle-, and low-dose Yangxue Rougan pill groups were given Yangxue Rougan pills at a dose of 9.5, 4.75, and 2.38 g/kg, respectively, those in the Fuzheng Huayu capsule group were given Fuzheng Huayu capsules at a dose of 0.75 g/kg, and those in the blank control group and the multi-factor model group were given an equal volume of distilled water by gavage every day for 6 consecutive weeks. The rats were treated at week 12. HE staining and Masson staining were used to observe the degree of liver fibrosis in rats, and PCR and Western blot were used to measure the expression of TGF-β1, Smad3, and Smad7 in the liver. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the Dunnett's t -test was used for further comparison between two groups. Results Compared with the blank control group, the multi-factor model group had a severely damaged lobular structure and a significantly higher degree of liver fibrosis, with the formation of pseudolobules with different sizes; compared with the multi-factor model group, the Yangxue Rougan pill groups had a significant improvement in the degree of liver fibrosis, with the most significant therapeutic effect in the high- and middle-dose Yangxue Rougan pill groups. Compared with the blank control group, the multi-factor model group had significant increases in the expression of TGF-β1 and Smad3 and a significant reduction in the expression of Smad7 in liver tissue (all P < 0.05); compared with the multi-factor model group, the Yangxue Rougan pill groups had a significant reduction in the expression of TGF-β1 and a significant increase in the expression of Smad7 (all P < 0.05); compared with the multi-factor model group, the high- and middle-dose Yangxue Rougan pill groups had a significant reduction in the expression of Smad3 (both P < 0.05). Conclusion Yangxue Rougan pills can significantly inhibit liver fibrosis in rats by downregulating the expression of TGF-β1 and Smad3 and upregulating the expression of Smad7, and therefore, the TGF-β1/Smad signaling pathway is one of the mechanisms of action of Yangxue Rougan pills in improving liver fibrosis.

12.
Journal of Clinical Hepatology ; (12): 1404-1408, 2021.
Article in Chinese | WPRIM | ID: wpr-877332

ABSTRACT

ObjectiveTo investigate the expression of L1 cell adhesion molecule (L1CAM) and transforming growth factor-β1 (TGFβ1) in pancreatic cancer tissue and their association with the prognosis of pancreatic cancer. MethodsHistological specimens were collected from 125 patients with pancreatic cancer who underwent surgical resection in The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University Cancer Hospital, and Wuming Hospital of Guangxi Medical University from January 2015 to January 2018. Immunohistochemistry was used to measure the expression of L1CAM and TGFβ1 in all specimens, and the association of the expression of L1CAM and TGFβ1 with clinical indices, survival, and prognosis was analyzed. The t-test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups; the Cox proportional-hazards regression model was used to investigate the influencing factors for the survival of patients with pancreatic cancer; the Kaplan-Meier survival analysis was used to evaluate the survival of patients with different expression levels of L1CAM and TGFβ1. ResultsThe high protein expression rate of L1CAM in pancreatic cancer tissue was significantly higher than that in adjacent tissue (75.20% vs 20.00%, χ2=76.352, P<0.001). The high protein expression rate of TGFβ1 in pancreatic cancer tissue was significantly higher than that in adjacent tissue (8160% vs 23.20%, χ2=85.461, P<0.001). The protein expression of L1CAM was positively correlated with that of TGFβ1 in pancreatic cancer (r=0.492, P<0.001). The protein expression of L1CAM and TGFβ1 were associated with tumor size, degree of tumor differentiation, TNM stage, lymph node metastasis, intravascular tumor thrombus, and perineural invasion (all P<0.05). The patients with high protein expression of L1CAM or TGFβ1 had a significantly lower overall survival rate than those with low expression (χ2=54661 and 39597, both P<0.001). ConclusionL1CAM and TGFβ1 proteins are highly expressed in pancreatic cancer tissue and may be associated with poor prognosis by promoting lymphatic metastasis and hematogenous metastasis. L1CAM and TGFβ1 proteins play an important role in the development, progression, and metastasis of pancreatic cancer.

13.
Chinese Journal of Nephrology ; (12): 911-917, 2021.
Article in Chinese | WPRIM | ID: wpr-911912

ABSTRACT

Objective:To investigate the role and mechanism of (histone deacetylase 6, HDAC6) in the epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells and the activation of renal interstitial fibroblasts.Methods:Human renal tubular epithelial cells (HK-2) and rat renal interstitial fibroblast (NRK-49F) were cultured in vitro, and divided into 4 groups: control group, Tubastatin A (TA) group (treated with 10 μmol/L HDAC6 inhibitor TA for 36 h), transforming growth factor-β1 (TGF-β1) group (10 ng/ml TGF-β1 for 36 h), and TGF-β1+TA group (treated with 10 ng/ml TGF-β1 and 10 μmol/L TA for 36 h). The expression levels of fibronectin, α-smooth muscle actin (α-SMA), collagen I, E-cadherin, HDAC6, acetyl histone H3, histone H3, acetyl α-tubulin, α-tubulin, TGF-β receptor (TGF-βR) 1, p-Smad3, Smad3, connective tissue growth factor (CTGF), epidermal growth factor receptor (EGFR) and p-EGFR in HK-2 and NRK-49F cell samples were detected by Western blotting, and quantitative analysis was performed according to gray level. Results:(1) In HK-2 cells stimulated by TGF-β1, TA decreased the expression of fibronectin, α-SMA, collagen I, and increased the expression of epithelial cell marker E-cadherin. Meanwhile, TA decreased the expression of HDAC6 and increased the expression levels of acetyl histone H3 and acetyl α-tubulin (all P<0.05). (2) Compared with the TGF-β1 group, the expressions of TGF-βR1, p-Smad3, CTGF and p-EGFR in TGF-β1+TA group were decreased (all P<0.05), while the total protein levels of Smad3 and EGFR were not significantly different (both P>0.05). (3) In NRK-49F cells stimulated by TGF-β1, TA decreased the expressions of fibronectin, α-SMA, collagen I, TGF-βR1 and p-Smad3 (all P<0.05). Conclusions:Blockade of HDAC6 by TA may inhibit the EMT of renal tubular epithelial cells and the activation of renal interstitial fibroblasts via regulating multiple signaling pathways including TGF-β/Smad3, CTGF and EGFR.

14.
Chinese Journal of Nephrology ; (12): 1001-1007, 2021.
Article in Chinese | WPRIM | ID: wpr-911920

ABSTRACT

Objective:To establish a rat model of neurogenic bladder and analyze the changes in kidney morphology and function and the expression of proteins in AngiotensinⅡ(AngⅡ)/transforming growth factor β1 (TGF-β1)/Smads pathway.Methods:Sprague-Dawley rats were randomly divided into experimental group (spinal nerve amputation, n=36) and control group (sham operation, n=12). At 6, 12, and 24 weeks, the bladder compliance was measured by cystometry, the kidney morphology was detected by B-ultrasound, blood urea nitrogen (BUN) and serum creatinine (Scr) in blood samples were examined, the kidney pathological changes were detected by Masson and HE staining, the distribution of AngⅡ/TGF-β1/Smads pathway proteins was analyzed by immunohistochemisty, and the protein expressions in kidney were detected by Western blotting. Results:Urodynamics showed that the basic bladder pressure in experimental group was higher than that in control group. B-ultrasound showed that compared with the control group, the diameter of the renal pelvis of the rats with nerve dissection gradually increased ( P<0.05), and the hydronephrosis was gradually obvious. Compared with the control group, the BUN and Scr in experimental group gradually increased (both P<0.01). Masson and HE staining showed that compared with the control group, the collagen expression and renal tubulointerstitial scores in experimental group were gradually increased (both P<0.01). Immunohistochemisty showed that compared with the control group, in experimental group the expression of angiotensinⅡ receptor type 1 (AT1), TGF-β receptor 1(TGF-βR1), phosphorylated Smad2 gradually increased (all P<0.01), the pathway inhibitor Smad6 gradually decreased ( P<0.01), and the distribution of each protein in kidney was consistent. Western blotting showed a corresponding expression trend with immunohistochemisty. Conclusions:In neurogenic bladder caused by bilateral spinal nerve amputation, due to bladder dysfunction, increased bladder pressure induces hydronephrosis, destruction of the nephron structure, activation of AngⅡ/TGF-β1/Smads pathway, and renal fibrosis. This method is effective and has clinical similarities, laying a foundation for exploring neurogenic bladder treatment.

15.
International Eye Science ; (12): 1962-1967, 2021.
Article in Chinese | WPRIM | ID: wpr-887394

ABSTRACT

@#AIM: To investigate the expression of different kinds of transforming growth factors beta- 1(TGF- β1)and changes of activin receptor-like kinase(ALK)in pterygium and normal conjunctiva tissues. <p>METHODS: A total of 40 cases(40 eyes)of pterygium patients who underwent surgical treatment in our hospital were selected. In the same period, 40 cases(40 eyes)of normal conjunctiva tissues removed from the eye due to cataract surgery were selected. The expression of TGF-β1 receptors(ALK1/ALK5)in pterygium and normal conjunctiva tissues was detected by immunohistochemistry, with the proportion of positive staining cells counted. The expression of ALK1 and ALK5 mRNA and their proteins were quantified by reverse transcription polymerase chain reaction(RT-PCR)and Western Blot, respectively.<p>RESULTS: According to immunohistochemistry results, the ALK1 expression level was increased more distinct in pterygium group, compared to the normal conjunctiva group, and it was detected throughout the full-thickness pterygium epithelial cells, while only in the basal layer of epithelial cells in normal conjunctiva tissues; the ALK5 was detected in the basal layer of epithelial cells in both groups, while its level was decreased in the pterygium group compared to normal conjunctiva group. There was significant difference in the proportion of ALK1 and ALK5 positive cells between the two groups(all <i>P</i><0.05). The expression of the ALK1 mRNA and its protein in the pterygium tissues were significantly elevated, while the ALK5 mRNA level and its protein was significantly decreased, compared with the normal conjunctival group(<i>P</i><0.05).<p>CONCLUSION: Compared with the normal conjunctiva tissues, the expression of ALK1 and ALK5 in pterygium tissues was increased and decreased, respectively. This indicated different activation status of TGF-β signaling pathway, providing experimental evidence for further study on the pathogenesis of pterygium.

16.
Acta cir. bras ; Acta Cir. Bras. (Online);36(6): e360604, 2021. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1284910

ABSTRACT

ABSTRACT Purpose Herein we evaluated the effects of platelet concentrate (PC) and platelet-poor plasma (PPP) on bone repair using noncritical defects in the calvaria of rabbits and compared them to the presence of TGF-β1 and osteocalcin on reparative sites. Methods Five noncritical defects of 8.7 mm in diameter were created on the calvaria of 15 animals. Each defect was treated differently, using autograft (ABG), ABG associated with PC (ABG + PC), ABG with PPP (ABG + PPP), isolated PPP, and blood clot (control). The animals were submitted to euthanasia on the second, fourth and sixth week post-surgery. Results The defects that received ABG+PC or PPP demonstrated lower bone formation when compared to specimens that received ABG in the same period. These results coincided to significant higher immunopositivity for TGF-β1 for specimens that received PC, and lower presence of cytokine in the group PPP. However, either higher or lower presence of TGF-β1 were also correlated to lower presence of osteocalcin. Likewise, these results were similar to findings in specimens treated only with PPP when compared to control. Conclusions PC and PPP were not effective when applied in association with ABG. Similarly, isolated use of PPP was not beneficial in optimizing the bone repair.


Subject(s)
Animals , Osteogenesis , Transforming Growth Factor beta1/metabolism , Rabbits , Skull/surgery , Osteocalcin , Autografts
17.
Article in Chinese | WPRIM | ID: wpr-865408

ABSTRACT

Objective: To evaluate the effect of resveratrol against CCl4-induced nephrotoxicity. Methods: Forty-two male Wistar rats were divided into seven groups randomly. After six weeks, kidney weight, body weight, blood urea, serum creatinine, oxidative stress markers, and gene expression of renal transforming growth factor-beta1 (TGF-β1), TGF-β receptor type 1 (TGF-βR1) and Smad3 were determined. In addition, the protein level of TGF-β1 in the tissue lysate was measured. Results: Resveratrol had a protective role in renal tissue by the improvement of antioxidant balance and reduction of renal parameters such as creatinine and urea (P<0.001). In addition, the renal mRNA level of TGF-β1, TGF-βR1, Smad3, as well as the protein level of TGF-β1 were decreased in rats treated with resveratrol (P<0.001), compared to the CCl4 group. Conclusions: Overall, resveratrol shows a protective effect against nephrotoxicity in CCl4 treated rats by reducing oxidative stress status and modulating the TGF-β signaling.

18.
Zhonghua laodong weisheng zhiyebing zazhi ; Zhonghua laodong weisheng zhiyebing zazhi;(12): 7-12, 2020.
Article in Chinese | WPRIM | ID: wpr-798629

ABSTRACT

Objective@#To investigate the effect of peroxiredoxin 2 (Prx2) overexpression on fibroblast proliferation and collagen synthesis induced by transforming growth factor-β1 (TGF-β1) .@*Methods@#Fibroblasts were randomly divided into control group (DMEM medium) , TGF-β1 group (5 μg/L TGF-β1) , negative control group (treated with 5 μg/L TGF-β1 and transfected with empty lentiviral vector) , and Prx2 group (treated with 5 μg/L TGF-β1 and transfected with Prx2 overexpression lentiviral vector) . MTT assay was used to measure cell proliferation, immunofluorescence assay was used to measure the expression of 8-OHdG, and Western blot was used to measure the expression of p-JNK, p-P38, collagen type I, collagen type III, and Prx2. SPSS 18.0 was used for statistical analysis. The continuous data were expressed as mean±standard deviation; an analysis of variance was used for comparison between groups, and the least significant difference t-test was used for further comparison between two groups.@*Results@#Lentiviral transfection was performed successfully, and the Prx2 group had a significant increase in the protein expression of Prx2 (P<0.05) . Compared with the control group, the TGF-β1 group had a significant increase in the proliferation ability (P<0.05) , and compared with the TGF-β1 group, the Prx2 group had a significant reduction in the proliferation ability (P<0.05) . Compared with the control group, the TGF-β1 group had significant increases in the expression of 8-OHdG, p-JNK, p-P38, collagen type I, and collagen type III (P<0.05) ; compared with the TGF-β1 group, the negative control group had no significant changes in the expression of 8-OHdG, p-JNK, p-P38, collagen type I, and collagen type III (P>0.05) , while the Prx2 group had significant reductions in the above parameters (P<0.05) .@*Conclusion@#Prx2 overexpression inhibits fibroblast proliferation and collagen synthesis induced by TGF-β1 through inhibiting reactive oxygen species and activating the JNK and P38 pathways.

19.
Article in Chinese | WPRIM | ID: wpr-847623

ABSTRACT

BACKGROUND: Liver fibrosis has higher morbidity and mortality. Activation and proliferation of hepatic stellate cells is a key link in the progression of liver fibrosis. At present, there are still no effective anti-fibrosis agents targeting single links or targets. OBJECTIVE: To analyze the effect of human adipose stem cells derived exosomes on rats with liver fibrosis induced by carbon tetrachloride. METHODS: Human adipose stem cells were obtained from healthy people by enzyme dissolution method. After in vitro culture, human adipose stem cells derived exosomes were obtained by multiple ultrafiltration. Different concentrations of exosomes were used to treat the hepatic stellate cells activated by transforming growth factor β1. The human adipose stem cells activated by transforming growth factor β1 were treated with different concentrations of exosomes. The expression of α-smooth actin in the cells was detected by quantitative PCR, and the growth and apoptosis of activated hepatic stellate cells were detected by CCK-8 and flow cytometry respectively. Rat models of liver fibrosis were established by intraperitoneal injection of carbon tetrachloride and treated by tail vein injection of exosomes. Rat liver function, serum levels of type III procollagen and type IV collagen, and Ishak score were determined. Semi-quantitative analysis of liver fibrosis was performed. The expression levels of tissue inhibitor of matrix metalloproteinase-1, matrix metalloproteinase 9 and α-smooth actin in liver tissue were measured by immunofluorescence method. The study protocol was approved by the Animal Ethics Committee and Medical Ethics Committee, Tongji University, China in January, 2017. RESULTS AND CONCLUSION: Human adipose stem cells derived exosomes inhibited the proliferation of activated hepatic stellate cells. The possible mechanism is to inhibit the proliferation of activated macrophages, reduce the production of collagen fibers, α-smooth actin actin, and tissue inhibitor of matrix metalloproteinase-1, and to increase the expression of matrix metalloproteinase 9. These findings suggest that exosomes can be used to treat carbon tetrachloride induced liver fibrosis.

20.
Article in Chinese | WPRIM | ID: wpr-847652

ABSTRACT

BACKGROUND: Studies have shown that the increase of bone resorption in osteoclasts over-activates transforming growth factor beta 1 (TGF-ß1), and uncouples bone resorption and bone formation, ultimately leading to a hardened phenotype of the subchondral bone In an animal model of osteoarthritis. Progression of osteoarthritis can be attenuated by inhibiting TGF-ß1 signaling pathway. OBJECTIVE: To detect whether osteoarthritis progression can be delayed by the local Injection of halofuglnone In Beagle models of osteoarthritis. METHODS: Eighteen male Beagle dogs were randomized into a sham (control) group, a model (osteoarthritis) group, or a treatment (halofuglnone) group. Animal models of osteoarthritis were made by anterior cruciate ligament transection in the latter two groups. Animals In the treatment group were given local injection of halofuglnone (37.8 ng) Into the subchondral bone. Serum levels of type II collagen C-terminal peptide (CTX-II) and type X collagen a1 chain (COLI 0A1) were measured at 4, 8,12, and 16 weeks after modeling. The Beagle dogs were sacrificed at the 16th week after surgery, and the alterations of microarchitecture of the subchondral bone were detected by micro-CT. Articular cartilage degeneration was graded using safranin О and fast green staining combined with the Osteoarthritis Research Society International (OARSI)-modified Manklng criteria. Immunostaining analyses were conducted to detect the expression levels of TGF-ß1 and matrix metalloprotelnase 13. The study protocol was approved by the Animal Ethics Committee of the First Affiliated Hospital of Xinjiang Medical University, with the approval No. IACUC20160304-07. RESULTS AND CONCLUSION: The COL10A1 level In the model group was higher than that in the control group and the treatment group at 8 and 12 weeks after modeling (P 0.05). Overall, local Injection of halofuginon attenuates anterior cruciate ligament transection-lnduced osteoarthritis by inhibiting abnormally elevated TGF-ß1 In the subchondral bone and blocking abnormal bone remodeling. Therefore, local Injection of halofuginon may be a new therapeutic alternative for osteoarthritis.

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