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Objective To explore the roles of MircroRNA-217 ( Mir-217 ) , silent information regulator 1 (Sirt1), and hypoxia-inducible factor-1α(HIF-1α)in high glucose-induced inflammation and fibrosis in rat glomerular mesangial cells( RMCs) . Methods RMCs were pre-incubated with a Sirt1 activator resveratrol prior to high glucose treatment or transfected with Sirt1 small interfering RNA( siRNA) , HIF-1αsiRNA, and Mir-217 inhibitor. Real-time PCR was used to analyze the expressions of Mir-217, Sirt1 mRNA, and HIF-1α mRNA; Western blot was used to observe the protein expressions of Sirt1, HIF-1α, connective tissue growth factor(CTGF), endothelin-1(ET-1), and fibronectin( FN) . Enzyme-linked immunosorbent assay was applied to detect protein expression of transforming growth factor-β1(TGF-β1)and vascular endothelial growth factor(VEGF). Results High glucose increased Mir-217, HIF-1α, CTGF, ET-1, FN, TGF-β1, and VEGF expressions(all P<0. 01), while decreased Sirt1 expression. In addition, Mir-217 gene silencing or 25μmol/L resveratrol suppressed high glucose-stimulated expressions of HIF-1α, CTGF, endothelin-1, FN, TGF-β1, and VEGF(all P<0. 01). Conclusion Mir-217 mediates high glucose-induced inflammation and fibrosis in RMCs via Sirt1/HIF-1αsignal pathway. This study provides new evidence to clarify the protective mechanisms of Sirt1 in diabetic nephropathy.
ABSTRACT
Objective To explore the associations of serum Mir-217 with silent information regulator 1 (Sirt1)and hypoxia-inducible factor-1α(HIF-1α)in type 2 diabetic patients with different urinary albumin excretion rates. Methods A total of 479 patients with type 2 diabetes were divided into normoalbuminuric(D1, n=181), microalbuminuric(D2, n=165), and macroalbuminuric(D3, n=133)subgroups. 192 normal subjects served as control group. Serum level of Mir-217 was detected by realtime PCR. Serum Sirt1, HIF-1α, and vascular endothelial growth factor ( VEGF ) levels were determined by enzyme-linked immunosorbent assay. Results Compared with control subjects, serum Mir-217 level was significantly increased in type 2 diabetic patients and gradually increased in D1, D2, and D3 groups(P<0. 01). The parameters of age, diabetes duration, body mass index, fasting plasma glucose, fasting insulin, homeostasis model assessment of insulin resistant index(HOMA-IR), HbA1C, low density lipoprotein-cholesterol( LDL-C) , total cholesterol ( TC ) , triglyceride ( TG ) , serum uric acid ( SUA ) , blood urea nitrogen(BUN), HIF-1α, VEGF, and Mir-217 all were positively correlated with ACR(all P<0. 05). High density lipoprotein-cholesterol(HDL-C)and Sirt1 were negatively correlated with ACR(both P<0. 05). VEGF, HIF-1α, Mir-217, BUN, diabetes duration, LDL-C, Sirt1, and SUA were independent factors that influenced ACR(all P<0. 01). Additionally, diabetes duration, HOMA-IR, HbA1C, ACR, LDL-C, TC, TG, SUA, BUN, HIF-1α, and VEGF were positively correlated with Mir-217(all P<0. 05), while Sirt1 was negatively correlated with Mir-217(P<0. 01). Conclusion Serum Mir-217, as a possible biomarker for early diagnosis of diabetic nephropathy, may be involved in the development of diabetic nephropathy by promoting chronic inflammatory reaction, renal fibrosis, and angiogenesis.
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Objective To investigate microRNA-217 expression and its significance in colorectal cancer.Methods MiR-217 expression was detected in 30 cases of colorectal cancer tissues and corresponding adjacent normal colorectal tissues by qRT-PCR.The clinicopathologic correlations of miR-217 expression were performed using Fisher's exact test.Kaplan-Meier method was used to evaluate the overall survival of patients.Results MiR-217 was significantly lower in colorectal cancer tissues than in normal colorectal tissues (P ＜ 0.01).Moreover,the decreased miR-217 level was significantly associated with tumor size and TNM stage,as well as lymph node and distant metastasis.Meanwhile,patients of colorectal cancer with low levels of miR-217 expression had a significantly shorter median survival (x2 =4.584,P ＜ 0.05) than those with high levels of miR-217 expression.Conclusions Downregulated miR-217 in colorectal cancer tissues correlates to poor prognosis in postoperative colorectal cancer patients.