Modulating secondary growth of perovskite grains through residual solvent evaporation.

Over the past decade, perovskite solar cells (PSCs) have attracted enormous attention due to their high performance. One key to fabricating high-quality perovskite films lies in controlling the volatilization rate of residual solvents during the annealing process. This study systematically investigates how different protective substrates affect the volatilization rate of residual solvent in perovskite films. By adjusting the direction and rate of evaporation, the supersaturation time of the solution was precisely controlled, leading to effective recrystallization of the grains. Concurrently, the annealing time was optimized to enhance film quality further. This optimization aimed to increase crystallinity, reduce defects, and thereby minimize non-radiative recombination centers. Implementing these methodologies, particularly the use of filter paper as a protective substrate during a 2-minute annealing process, significantly improved the fill factor (FF) and open-circuit voltage (VOC) of the PSCs. This led to a remarkable 5.26% improvement in power conversion efficiency (PCE) compared to control devices. The strategies employed in this work demonstrate significant potential in improving PSC film quality. This approach not only advances our understanding of film formation dynamics but also provides a practical guideline for future PSC fabrication.

Genetic association study of TERT gene variants with chronic kidney disease susceptibility in the Chinese population.

The incidence and mortality of chronic kidney disease (CKD) are increasing globally. Studies have demonstrated the significance of genetic risk factors in the progression of CKD. Telomerase reverse transcriptase (TERT) may be implicated in the development of CKD. This study aimed to investigate the correlation between TERT gene variants and susceptibility to CKD in the Chinese population. A total of 507 patients with CKD and 510 healthy controls were recruited for this case-control study. Four candidate loci were identified using the MassARRAY platform. Logistic regression analysis was employed to assess the association between TERT gene variants and the risk of CKD. The false positive reporting probability (FPRP) method was utilized to evaluate the validity of statistically significant associations. The multifactorial dimensionality reduction (MDR) method was used to evaluate the interaction between SNPs and the risk of CKD. Furthermore, discrepancies in the clinical features of subjects with diverse genotypes were evaluated using one-way analysis of variance (ANOVA). Our findings revealed a correlation between rs2735940 and rs4635969 and an increased risk of CKD. Stratification analysis indicated that rs4635969 was related to an increased risk of CKD in different subgroups (age ≤ 50 years and male). MDR analysis indicated that the two-site model (rs2735940 and rs4635969) was the best prediction model. Furthermore, the rs2735940 GG genotype was found to be linked to an increased level of microalbuminuria (MAU) in patients with CKD. Our study is the first to reveal a connection between TERT gene variants and susceptibility to CKD, providing new insights into the field of nephrology.

lncRNA TUG1 regulates hyperuricemia-induced renal fibrosis in a rat model.

Renal fibrosis is most common among chronic kidney diseases. Molecular studies have shown that long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) participate in renal fibrosis, while the roles of lncRNA taurine upregulated gene 1 (TUG1) and miR-140-3p in hyperuricemia-induced renal fibrosis remain less investigated. In this study, a rat hyperuricemia model is constructed by oral administration of adenine. TUG1, miR-140-3p, and cathepsin D (CtsD) expression levels in rat models are measured. After altering TUG1, miR-140-3p, or CtsD expression in modelled rats, biochemical indices, including uric acid (UA), serum creatine (SCr), blood urea nitrogen (BUN), and 24-h urine protein are detected, pathological changes in the renal tissues, and renal fibrosis are examined. In renal tissues from hyperuricemic rats, TUG1 and CtsD are upregulated, while miR-140-3p is downregulated. Inhibiting TUG1 or CtsD or upregulating miR-140-3p relieves renal fibrosis in hyperuricemic rats. Downregulated miR-140-3p reverses the therapeutic effect of TUG1 reduction, while overexpression of CtsD abolishes the role of miR-140-3p upregulation in renal fibrosis. Collectively, this study highlights that TUG1 inhibition upregulates miR-140-3p to ameliorate renal fibrosis in hyperuricemic rats by inhibiting CtsD.

Potential signaling pathway through which Notch regulates oxidative damage and apoptosis in renal tubular epithelial cells induced by high glucose.

Diabetic nephropathy (DN) is one of the most common and serious complications of diabetes mellitus, and glomerular sclerosis and renal tubular interstitial fibrosis are the main pathological features. Current evidence indicates that the Notch pathway can mediate the impairment of renal tubular function and induce angiogenesis and renal interstitial fibrosis. This study was conducted to explore the potential signaling pathway through which Notch regulates oxidative damage and apoptosis in renal tubular epithelial cells induced by high glucose. mRNA and protein expression levels were assessed using real-time PCR and Western blot, respectively. The protein expression levels of Jaggedl, Notchl, pro-caspase-3, Drpl, and PGC-1α were increased by high glucose, but N-[N-(3,5-difluorohenacetyl)-l-alanyl]-S-phenylglycine tert-butyl ester (DAPT; an inhibitor of the Notch signaling pathway) reversed these effects. Furthermore, DAPT reduced the mRNA expression of Jaggedl, Notchl, MnSOD2, Drpl, and PGC-1α in renal tubular epithelial cells induced by high glucose. In conclusion, the Notch signaling pathway may regulate oxidative damage and apoptosis in renal tubular epithelial cells induced by high glucose by regulating mitochondrial dynein and biogenesis genes, which can accelerate renal interstitial fibrosis in DN. The Notch signaling pathway might be a potential therapeutic target for DN, and DAPT might become a potential drug for the treatment of DN.

Genetic Variations rs859, rs4646, and rs372883 in the 3'-Untranslated Regions of Genes Are Associated with a Risk of IgA Nephropathy.

BACKGROUND: Previous studies indicate that genetic factors play an important role in the pathogenesis of IgA nephropathy (IgAN). To evaluate the association between single nucleotide polymorphisms (SNPs) in the 3'-untranslated region (3'-UTR) of genes and IgAN risk, we performed a case-control study in a Chinese Han population. MATERIALS: Twelve SNPs were selected and genotyped in 384 IgAN patients and 357 healthy controls. Odds ratio (OR) and 95% confidence intervals (CI) were calculated by logistic regression adjusted for age and gender. Multifactor dimensionality reduction (MDR) was used to analyze the interaction of SNP-SNP with IgAN risk. RESULTS: Our study demonstrated that IL-16 rs859 (OR = 0.75, p = 0.040) and CYP19A1 rs4646 (OR = 2.58, p = 0.017) polymorphism were related to the risk of IgAN. In stratified analyses by gender, CYP19A1 rs4646 (OR = 2.96, p = 0.015) and BACH1 rs372883 (OR = 1.81, p = 0.038) polymorphisms conferred susceptibility to IgAN in males. Besides, rs372883 reduced IgAN risk in females (OR = 0.44, p = 0.042). We also found rs859 polymorphism was correlated with grade I-II (OR = 0.42, p = 0.028) in subgroup analysis of Lee's classification. Additionally, we found rs4646 polymorphism was correlated with serum creatinine (p = 0.035). CONCLUSION: Our results suggested that the IL-16 rs859, CYP19A1 rs4646, and BACH1 rs372883 polymorphisms have potential roles in the genetic susceptibility to IgAN in Chinese Han population.

Rapamycin- and starvation-induced autophagy are associated with miRNA dysregulation in A549 cells.

MicroRNAs (miRNAs) are short (20-23 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. In recent years, deep sequencing of the transcription is being increasingly utilized with the promise of higher sensitivity for the identification of differential expression patterns as well as the opportunity to discover new transcripts, including new alternative isoforms and miRNAs. In this study, miRNAs from A549 cells treated with/without rapamycin or starvation were subject to genome-wide deep sequencing. A total of 1534 miRNAs were detected from the rapamycin- and starvation-treated A549 cells. Among them, 31 miRNAs were consistently upregulated and 131 miRNAs were downregulated in the treated cells when compared with the untreated cells. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis of the predicted target genes of the most significantly differentially expressed miRNAs revealed that the autophagy-related miRNAs are involved in cancer pathway. Taken together, our findings indicate that the underlying mechanism responsible for autophagy is associated with dysregulation of miRNAs in rapamycin- or starvation-induced A549 cells.

Evaluation of the pharmacokinetics, tissue distribution and excretion studies of YMR-65, a tubulin polymerization inhibitor with potential anticancer activity, in rats using UPLC-MS/MS.

1. YMR-65, 5-(5-bromo-1-methyl-1H-indol-3-yl)-3-(3-methoxyphenyl)-4, 5-dihydro-1H-pyrazole-1-carboxamide, is a new tubulin polymerization inhibitor with encouraging anticancer activity. 2. The validated ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) method was successfully applied to the pharmacokinetics, tissue distribution and excretion study of YMR-65 after oral and intravenous administration. The area under concentration-time curve (AUC0-∞) for YMR-65 were 151.67 ± 54.48 and 459.45 ± 49.23 ng/ml*h for oral and intravenous administration at the dosage of 1.5 mg/kg, respectively and the oral bioavailability was about 33.01%. Moreover, YMR-65 was extensively distributed in heart, liver, spleen, lung, kidney, stomach, intestine and testis and the highest were detected in heart, followed by stomach, intestine and liver. The majority of YMR-65 was excreted via feces and its accumulative excretion ratio during the period of 96 h was 19.83 ± 3.01%, but only 1.54 ± 0.37 and 0.215 ± 0.026% for urine within 96 h and bile within 10 h after intravenous administration, respectively, though the fecal and urine excretion were incomplete within 96 h. 3. In summary, this study defined the pharmacokinetic characteristics of YMR-65 in vivo and the important data can be a useful resource for further research and development.

Association of Interleukin-10 Polymorphisms (rs1800872, rs1800871, and rs1800896) with Predisposition to IgA Nephropathy in a Chinese Han Population: A Case-Control Study.

BACKGROUND/AIMS: IgA nephropathy (IgAN) is a common form of primary glomerulonephritis worldwide. Previous studies indicated that IL-10 single nucleotide polymorphisms (SNP) play an important role in IgAN pathogenesis, but the results were controversy. This study aimed to investigate the association between IL-10 SNPs (rs1800872, rs1800871, and rs1800896) with IgAN in a Chinese Han population. METHODS: We conducted a case-control study that included 351 patients with IgAN and 310 age-, gender- and ethnicity-matched healthy controls. Three promoter SNPs (rs1800872, rs1800871, and rs1800896) of IL-10 were genotyped by Sequenom MassARRAY. Odds ratios (ORs) with 95% confidence intervals (CI) were used to assess the relationship with IgAN. RESULTS: We found that the rs1800896 did not correlate with IgAN risk, whereas rs1800872 and rs1800871 were significantly associated with increased IgAN risk in all genetic models. The haplotype analysis indicated that the CCA haplotype was associated with increased IgAN risk (OR = 1.36; 95% CI = 1.05-1.75). Moreover, there were no associations between these SNPs and blood pressure or gender, whereas the rs1800896 variant was correlated with higher 24-hour urine protein in patients with IgAN. CONCLUSION: Taken together, these results suggest that IL-10 is a susceptibility gene in patients with IgAN.

The Endothelial Nitric Oxide Synthase Gene Polymorphism is Associated with the Susceptibility to Immunoglobulin a Nephropathy in Chinese Population.

BACKGROUND/AIMS: Endothelial nitric oxide synthase (eNOS) is one of the most important enzymes for producting nitric oxide (NO), which regulate the function of many organs and cells. The single nucleotide polymorphisms (SNPs) of eNOS were found to be associated with many kidney diseases. However, it is lack of relevant studies to evaluate the associations between eNOS polymorphisms and immunoglobulin A nephropathy (IgAN). This case-control study aimed to evaluate the relationship between eNOS polymorphisms and IgAN. METHODS: We recruited 351 IgAN patients and 310 age- and sex-matched healthy controls from Northwest China. Sequenom MassARRAY was used to detect the genotypes of two common eNOS SNPs (rs1799983 and rs2070744). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by the Chi square test to evaluate the associations between eNOS and IgAN. Phase 2.1 was used to conduct haplotype analysis. RESULTS: In the overall analysis, we found that the rs1799983 polymorphism was associated with a decreased risk of IgAN (G/T vs. G/G: OR=0.57, 95%CI=0.34-0.96; G/T+T/T vs. G/G: OR=0.52, 95%CI=0.31-0.86; G/T vs. G/G-T/T: OR=0.60, 95%CI=0.36-0.99; Log-additive model: OR=0.48, 95%CI=0.30-0.78). Haplotype analysis indicated that Trs1799983Crs2070744 is a protective factor against IgAN (OR=0.62, 95%CI=0.42--0.92). However, no significant differences were found between the two SNPs (rs1799983 and rs2070744) and clinical features (age, sex, blood pressure, and Lee's grade) of IgAN. CONCLUSION: The eNOS gene rs1799983 polymorphism and Trs1799983Crs2070744 haplotype may reduce the risk of IgAN in Chinese populations.

Fasudil inhibits tissue factor and plasminogen activator Inhibitor-1 secretion by peripheral blood mononuclear cells in CAPD patients.

Disturbances in hemostasis are common complications of kidney diseases and correlate well with cardiovascular mortality. Little is known about the effects of fasudil on tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) expression in peripheral blood mononuclear cells (PBMCs) in CAPD patients. PBMCs were isolated from 13 individuals with CAPD and 13 healthy subjects. After 4 h of incubation with or without LPS (10 ng/mL), TF and PAI-1 mRNA of PBMCs were detected by RT-PCR. The levels of TF and PAI-1 in culture supernatants of PBMCs were determined by ELISA. Compared with healthy controls, CAPD patients had increased TF, PAI-1 protein and mRNA expression by PBMCs at baseline and after stimulated by LPS (10 ng/mL) [p < 0.001]. The fasudil treatment resulted in a significant effect in decreasing TF and PAI-1 [p < 0.05] synthesis in PBMCs. TF and PAI-1 mRNA expression and activities in PBMCs were increased in CAPD patients. Fasudil reduced LPS-mediated TF and PAI-1 expression and activity in PBMCs. These effects may partially be relevant to the clinical benefits of fasudil in the treatment of CAPD patients.

MicroRNA-34a inhibits the proliferation and promotes the apoptosis of non-small cell lung cancer H1299 cell line by targeting TGFßR2.

MicroRNAs (MiRNAs) are small non-coding RNA molecules which act as important regulators of post-transcriptional gene expression by binding 3'-untranslated region (3'-UTR) of target messenger RNA (mRNA). In this study, we analyzed miRNA-34a (miR-34a) as a tumor suppressor in non-small cell lung cancer (NSCLC) H1299 cell line. The expression level of miR-34a in four different NSCLC cell lines, H1299, A549, SPCA-1, and HCC827, was significantly lower than that in the non-tumorigenic bronchial epithelium cell line BEAS-2B. In human NSCLC tissues, miR-34a expression level was also significantly decreased in pT2-4 compared with the pT1 group. Moreover, miR-34a mimic could inhibit the proliferation and triggered apoptosis in H1299 cells. Luciferase assays revealed that miR-34a inhibited TGFßR2 expression by targeting one binding site in the 3'-UTR of TGFßR2 mRNA. Quantitative real-time PCR (qRT-PCR) and Western blot assays verified that miR-34a reduced TGFßR2 expression at both mRNA and protein levels. Furthermore, downregulation of TGFßR2 by siRNA showed the same effects on the proliferation and apoptosis as miR-34a mimic in H1299 cells. Our results demonstrated that miR-34a could inhibit the proliferation and promote the apoptosis of H1299 cells partially through the downregulation of its target gene TGFßR2.

MiR-181a-5p inhibits cell proliferation and migration by targeting Kras in non-small cell lung cancer A549 cells.

MicroRNAs play important roles in carcinogenesis and tumor progress. Lung cancer is the leading cause of cancer mortality worldwide. In this study, the function of miR-181a-5p was investigated in non-small-cell lung cancer (NSCLC). Results showed that miR-181a-5p was significantly decreased in NSCLC tissues and cell lines. The proliferation and migration of A549 cells transfected with miR-181a-5p mimic was significantly inhibited. Luciferase activity assay results demonstrated that two binding sites of Kras could be directly targeted by miR-181a-5p. Furthermore, Kras was down-regulated by miR-181a-5p at both transcriptional and translational levels. SiRNA-mediated Kras down-regulation could mimic the effects of miR-181a-5p mimic in A549 cells. Our findings suggest that miR-181a-5p plays a potential role in tumor suppression by partially targeting Kras and has the potential therapeutic application in NSCLC patients.

Evodiamine might inhibit TGF-beta1-induced epithelial-mesenchymal transition in NRK52E cells via Smad and PPAR-gamma pathway.

Epithelial-mesenchymal transition (EMT) is involved in renal tubulointerstitial fibrosis. Transforming growth factor (TGF)-beta1 is the main inducer of EMT. Phosphorylation of Smad proteins and PPAR-gamma activation are required for the process of TGF-beta1-induced EMT. Evodiamine possesses anti-inflammatory, anti-obesity, anti-cancer, and anti-nociceptive effects. We have examined the effects of evodiamine in EMT induced by TGF-beta1 and the role of Smad and PPAR-gamma signal pathway in rat renal proximal tubular epithelial (NRK52E) cells in vitro. E-cadherin, alpha-smooth muscle actin (SMA), Smad 2 and PPAR-gamma mRNA and protein expressions were detected by real-time PCR and Western blot, respectively. NRK52E treated with TGF-beta1 for 48 h induced EMT, as evidenced by loss of E-cadherin and de novo expression of alpha-SMA. EMT was almost completely blocked by evodiamine and rosiglitazone. TGF-beta1 significantly increased Smad 2 expression and decreased PPAR-gamma expression in NRK52E cells compared with the control group, while evodiamine and rosiglitazone almost reversed these effects. These observations suggest that evodiamine and rosiglitazone inhibit TGF-beta1-induced EMT in NRK52E cells. Smad 2 and PPAR-gamma signal pathway might participate in the effects of evodiamine and rosiglitazone in EMT induced by TGF-beta1.

PKM2 promotes glioma progression by mediating CTNNB1 expression.

BACKGROUND: Glioma is a common intracranial tumor, exhibiting a high degree of aggressiveness and invasiveness. Pyruvate kinase M2 (PKM2) is overexpressed in glioma tissues. However, the biological role of PKM2 in glioma is unclear. METHODS: The qRT-PCR, CCK-8, Transwell, flow cytometry detection, western blot assays, ELISA assay, and pyruvate kinase activity assays were performed in glioma cells transfected with PKM2 shRNA to explore the function of PKM2 in glioma progression. Then, STRING website was used to predict the proteins that interacted with PKM2, and Co-IP assay was conducted to further validate their interaction. Subsequently, the above experiments were performed again to find the effect of catenin beta 1 (CTNNB1) overexpression on PKM2-deficient glioma cells. The transplanted tumor models were also established to further validate our findings. RESULTS: PKM2 was up-regulated in glioma cells and tissues. After inhibiting PKM2, the proliferation, migration, glycolysis, and EMT of glioma cells were significantly decreased, and the proportion of apoptosis was increased. The prediction results of STRING website showed that CTNNB1 and PKM2 had the highest interaction score. The correlation between CTNNB1 and PKM2 was further confirmed by Co-IP test. PKM2 knockdown suppressed glioma cell proliferation, migration, glycolysis, and EMT, while CTNNB1 overexpression rescued these inhibitory effects. Correspondingly, PKM2 knockdown inhibited glioma growth in vivo. CONCLUSION: In summary, these findings indicated that PKM2 promotes glioma progression by mediating CTNNB1 expression, providing a possible molecular marker for the clinical management of gliomas.

Fasudil attenuates oxidative stress-induced partial epithelial-mesenchymal transition of tubular epithelial cells in hyperuricemic nephropathy via activating Nrf2.

Anti-partial epithelial-mesenchymal transition (pEMT) treatment of renal tubular epithelial cells (TECs) represents a promising therapeutic approach. Hyperuricemia nephropathy (HN) arises as a consequence of hyperuricemia (HUA)-induced tubulointerstitial fibrosis (TIF). Studies have suggested that the Ras homolog member A (RhoA)/Rho-associated kinase (ROCK) pathway is a crucial signaling transduction system in renal fibrosis. Fasudil, a RhoA/ROCK inhibitor, has exhibited the potential to prevent fibrosis progress. However, its impact on the pEMT of TECs in HN remains unclear. Here, an HN rat model and an uric acid (UA)-stimulated human kidney 2 (HK2) cell model were established and treated with Fasudil to explore its effects. Furthermore, the underlying mechanism of action involved in the attenuation of pEMT in TECs by Fasudil during HN was probed by using multiple molecular approaches. The HN rat model exhibited significant renal dysfunction and histopathological damage, whereas in vitro and in vivo experiments further confirmed the pEMT status accompanied by RhoA/ROCK pathway activation and oxidative stress in tubular cells exposed to UA. Notably, Fasudil ameliorated these pathological changes, and this was consistent with the trend of ROCK silencing in vitro. Mechanistically, we identified the Neh2 domain of nuclear factor erythroid 2-related factor 2 (Nrf2) as a target of Fasudil for the first time. Fasudil targets Nrf2 activation and antagonizes oxidative stress to attenuate the pEMT of TECs in HN. Our findings suggest that Fasudil attenuates oxidative stress-induced pEMT of TECs in HN by targeting Nrf2 activation. Thus, Fasudil is a potential therapeutic agent for the treatment of HN.

Crystallinity Control and Strain Release in Wide-Bandgap Perovskite Film via Seed-Induced Growth for Efficient Photovoltaics.

The seed method stands out as a straightforward and efficient approach for fabricating high-performance perovskite solar cells (PSCs). In this study, we propose the utilization of an antisolvent as an additive to induce crystal seeding, thereby facilitating the growth of wide-bandgap perovskite grains. Specifically, we introduce three commonly used antisolvents─ethyl acetate (EA), isopropanol (IPA), and chlorobenzene (CB)─directly into the perovskite precursor solution to generate perovskite seeds, which serve to promote subsequent nucleation. This antisolvent-crystal seeding method (ACSM) results in increased grain sizes, reduced film defects, and overall improved film quality. Consequently, the power conversion efficiencies (PCEs) of 1.647 eV PSCs with EA, IPA, and CB additives are recorded at 19.86%, 20.61%, and 20.45%, respectively, surpassing that of the reference device with a PCE of 18.83%. Furthermore, the stability of the PSCs prepared through ACSM is notably enhanced. Notably, PSCs optimized with IPA retain 75% of the original PCE after being stored in ambient air conditions (25 °C, RH ∼ 15%) for 30 days, better than the CB-added (64%) and the EA-added devices (53%), while the reference devices only retain 31% of the initial PCE. Moreover, even after continuous thermal annealing at 50 °C for 200 h, IPA-assisted devices demonstrate the best stability, followed by those with CB and EA, with the reference exhibiting the poorest stability.

Global trends in colorectal cancer and metabolic syndrome research: a bibliometric and visualization analysis.

Numerous studies have demonstrated a robust correlation between metabolic syndrome (MetS) and colorectal cancer (CRC). Nonetheless, no systematic analysis or visualization of relevant publications has been conducted via bibliometrics. This research, centred on 616 publications obtainable through the Web of Science Core Collection (WoSCC), employed CiteSpace software and VOSviewer software for correlation analyses of authors, journals, institutions, countries, keywords, and citations. The findings indicate that the Public Library of Science had the highest number of publications, while the United States, China, and South Korea were the most contributory nations. Recent years have seen the mechanisms linking Metabolic Syndrome with Colorectal Cancer, including diet, obesity, insulin resistance, and intestinal flora, remain a burgeoning research area. Furthermore, bariatric surgery appears to be a promising new area of study. This paper presents the initial bibliometric and visualization analysis of research literature concerning CRC and MetS which examines research trends and hotspots.

Mucins 1-shRNA inhibit the proliferation and HIF-1alpha protein expression on human cholangiocarcinoma cells.

To explore the effects of Mucins (MUC)1-shRNA on the proliferation and hypoxia inducible factor (HIF)-1alpha expression of human cholangiocarcinoma (CCA) QBC939 cells in vitro. MUC1-shRNA was constructed and transfected with Lipofectamine™ 2000 into cultured CCA cells. MUC1 mRNA and protein expression levels were determined by RT-PCR and Western blot, respectively. The cellular proliferation and HIF-1alpha expression of QBC939 cells were evaluated by the MTT assay and Western blot, respectively. After transfection, the expression levels of MUC1 mRNA and protein in the experimental group decreased significantly in QBC939 (P < 0.01). The proliferation of MUC1 shRNA-transfected group was 0.30 ± 0.05, 38.32 ± 1.43%, 15.18 ± 1.32%, and there were remarkable differences when compared with the control groups (P < 0.05). Significant inhibition of HIF-1alpha protein expression in MUC1 shRNA-transfected group was also discovered (P < 0.05). MUC1-shRNA could inhibit proliferation and significantly weaken HIF-1alpha protein expression of QBC939 cells, suggesting its potential as a therapeutic target of CCA.

AEG-1 participates in TGF-beta1-induced EMT through p38 MAPK activation.

Epithelial-mesenchymal transition (EMT) is an important cellular event in organogenesis, cancer and renal tubulointerstitial fibrosis. Transforming growth factor-beta1 (TGF-beta1) is the key inducer of EMT and the p38 mitogen-activated protein kinases (p38 MAPK), an major intracellular signal transduction pathway is involved in TGF-beta1-induced EMT. Astrocyte elevated gene-1 (AEG-1) represents an chief genetic determinant regulating multiple events in tumorigenesis. Our present study is to explore the role of AEG-1 in TGF-beta1-induced p38 MAPK activation and EMT process in human renal tubular epithelial (HK-2) cells. The protein expressions of AEG-1, the markers of EMT and p38 phosphorylation were measured by Western blot. The protein expression of AEG-1 was increased in HK-2 cells treated with TGF-beta1. Knockdown of AEG-1 potently inhibited phosphorylation of p38 MAPK and reversed TGF-beta1-induced EMT. Over-expression of AEG-1 via AEG-1 transfection elicited p38 MAPK phosphorylation and promoted EMT. The effects of AEG-1 during EMT were blocked by a p38-specific inhibitor. Our findings suggest that AEG-1 plays an important role in TGF-beta1-induced EMT through activation of p38 MAPK in proximal tubular epithelial cells.

Rho kinase pathway is likely responsible for the profibrotic actions of aldosterone in renal epithelial cells via inducing epithelial-mesenchymal transition and extracellular matrix excretion.

It has been demonstrated that aldosterone (ALD) plays a direct profibrotic role in the kidney but the underlying mechanism remains unclear. We examined the role of Rho kinase signal pathway in epithelial-mesenchymal transition (EMT) process and extracellular matirx (ECM) synthesis induced by ALD in human renal proximal tubular epithelial (HK-2) cells in vitro. Rho kinase and collagen I, III protein expressions were detected by ELISA. E-cadherin, α-smooth muscle actin (SMA), collagen_I and collagen III mRNA expressions were detected by real time PCR. E-cadherin, and α-SMA protein expressions were measured by Western blot. Our results showed that ALD could significantly activate the Rho kinase in HK-2 cells, while in the presence of mineralocorticoid receptor (MR) antagonist eplerenone and Rho kinase inhibitor Y27632, the Rho kinase protein expression were almost completely prevented. Exposure of HK-2 cells to ALD for 48 h induced EMT as evidenced by loss of E-cadherin, and de novo expression of α-SMA. The EMT was completely blocked by eplerenone and Y27632. Meanwhile, ALD could significantly increase the mRNA and protein expressions of collagen I, III in HK-2 cells when compared with the control group, while eplerenone and Y27632 could almost reverse these effects. These observations suggest that ALD can activate Rho kinase pathway and Rho kinase pathway is likely responsible for the profibrotic actions of ALD in renal proximal tubular epithelial cells via inducing EMT and ECM excretion.