Liraglutide Suppresses Myocardial Fibrosis Progression by Inhibiting the Smad Signaling Pathway.

OBJECTIVE: Liraglutide is a commonly used hypoglycemic agent in clinical practice, and has been demonstrated to have protective effects against the development of cardiovascular disease. However, its potential role in myocardial fibrosis remains unexplored. The present study aims to assess the impact of liraglutide on the activation of cardiac fibroblasts. METHODS: Primary rat adult fibroblasts were isolated, cultured, and randomly allocated into 4 groups: control group, transforming growth factor beta1 (TGFß1) stimulation group, liraglutide group, and TGFß1+liraglutide group. Fibroblast activation was induced by TGFß1. Cell proliferation activity was assessed using the CKK-8 kit, and cellular activity was determined using the MTT kit. Reverse transcrition-quantitative polymerase chain reaction (RT-qPCR) was utilized to quantify the level of collagen transcription, immunofluorescence staining was performed to detect the expression level of type III collagen and α-smooth muscle protein (α-SMA), and immunoblotting was conducted to monitor alterations in signal pathways. RESULTS: The addition of 10, 25, 50 and 100 nmol/L of liraglutide did not induce any significant impact on the viability of fibroblasts (P>0.05). The rate of cellular proliferation was significantly higher in the TGFßl stimulation group than in the control group. However, the treatment with 50 and 100 nmol/L of liraglutide resulted in the reduction of TGFßl-induced cell proliferation (P<0.05). The RT-qPCR results revealed that the transcription levels of type I collagen, type III collagen, and α-SMA were significantly upregulated in the TGFßl stimulation group, when compared to the control group (P<0.05). However, the expression levels of these aforementioned factors significantly decreased in the TGFßl+liraglutide group (P<0.05). The immunofluorescence staining results revealed a significant increase in the expression levels of type III collagen and α-SMA in the TGFßl stimulation group, when compared to the control group (P<0.05). However, these expression levels significantly decreased in the TGFßl+liraglutide group, when compared to the TGFßl stimulation group (P<0.05). The Western blotting results revealed that the expression levels of phosphorylated smad2 and smad3 significantly increased in the TGFßl stimulation group, when compared to the control group (P<0.05), while these decreased in the TGFßl+liraglutide group (P<0.05). CONCLUSION: Liraglutide inhibits myocardial fibrosis development by suppressing the smad signaling pathway, reducing the activation and secretion of cardiac fibroblasts.

CTRP1 Attenuates UUO-induced Renal Fibrosis via AMPK/NOX4 Pathway in Mice.

C1q/TNF-related protein 1 (CTRP1), a conserved protein of the C1q family, plays a key role in cardiovascular and metabolic diseases. However, the role of CTRP1 in renal injury is unclear. The purpose of this study is to explore the role of CTRP1 in unilateral ureteral obstruction (UUO)-induced renal fibrosis and to elucidate the underlying mechanism. Using gene delivery system, CTRP1 was overexpressed in the kidney, then the mice were operated to induce UUO model after adenovirus transfection. It was found that the expression of CTRP1 in the renal tissue was decreased in mice after UUO. CTRP1 overexpression decreased the kidney function and kidney weight index. Moreover, CTRP1 reduced oxidative stress and renal collagen deposition in vivo. As expected, we found that CTRP1 activated AMP-activated kinase (AMPK) and decreased NOX4 expression, while silencing AMPKα1 abolished the protective effects of CTRP1 overexpression in mice after UUO. In conclusion, CTRP1 may protect against UUO-induced renal injury via AMPK/NOX4 signaling. Our results indicate that CTRP1 exhibits potential effects to treat renal fibrosis caused by UUO.

Long non coding RNA XIST as a prognostic cancer marker - A meta-analysis.

BACKGROUND: The X inactivate-specific transcript (XIST), derived from XIST gene, is aberrantly expressed in various cancers. High-expression of XIST is related to poor clinical outcome. This meta-analysis evaluated the potential role of XIST as novel predictor of prognosis in human cancer. MATERIALS AND METHODS: This meta-analysis collected eligible studies about XIST and tumor prognosis through retrieving keywords in Web of Science, PubMed, Embase and the CNKI database, from 1993 to August 21, 2017. The quantitative meta-analysis was carried out with Stata SE12.0 and RevMan3.23 software. The aim was to determine whether XIST expression is associated with cancer prognosis and clinicopathology. RESULTS: A total of 858 patients from 10 eligible studies were included in the final meta-analysis. Overall, a significant negative association between XIST and overall survival (OS) time (HR = 2.62, 95% CI: 2.18-3.14) was observed. Statistical significance was also showed in subgroup meta-analysis stratified by the country, sample size, follow-up and publication year. It was reported that increased XIST was positively related to advanced clinical TNM stage (OR = 4.03, 95% CI: 2.22-7.30), lymph node metastasis (LNM) (OR = 2.70, 95% CI: 1.73-4.21), distant metastasis (DM) (OR = 2.61, 95% CI: 1.57-4.33) and tumor size (OR = 3.10, 95% CI: 2.24-4.30). CONCLUSIONS: LncRNA XIST may serve as a potential biomarker to predict solid tumor prognosis. This molecule can be effectively used to predict the clinical and pathological features of cancers.