ABSTRACT
Objective To explore the expression of miroRNA-21 (miRNA-21) in myocardial fibroblasts stimulated by indoxyl sulfate (IS) and its role on paracrine factors of myocardial fibroblasts.Methods Myocardial fibroblasts which derived from C57BL/6J mice were divided into control group and IS group,and their expressions of miRNA-21 were detected by real time PCR after 48 h.MiRNA-21 inhibitor transfection was applied to silence miRNA-21 expression.Myocardial fibroblasts were divided into creatinine (Scr) group (Scr treated for 48 h),Scr+IS group (Scr and 50 μmol/L IS treated for 48 h),Scr+miRNA-21 inhibitor group (miRNA-21 inhibitor treated for 24 h and then Scr treated for 48 h) and Scr+miRNA-21 inhibitor+ IS group (miRNA-21 inhibitor pretreated for 24 h and then Scr and IS treated for 48 h).Enzyme-linked immunosorbent assay was performed to evaluate the expressions of interleukin-1 (IL-1),interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α).Western blotting was applied to detect the expressions of transforming growth factor-β (TGF-β),matrix metalloproteinases 2 (MMP2),matrix metalloproteinases 9 (MMP9) and tissue inhibitor of metalloproteinases 1 (TIMP1).Results The expression of miRNA-21 was obviously increased in IS group than that in control group (P ＜ 0.01).Compared with those in Scr group,the expressions of IL-1,IL-6,TNF-α,TGF-β,MMP2 and MMP9 significantly increased (all P ＜ 0.05),while the expression of TIMP1 decreased (P ＜ 0.05).When the expression of miRNA-21 was inhibited,the expressions of IL-1,IL-6,TNF-α,TGF-β and MMP2 in Scr+miRNA-21 inhibitor+IS group significantly decreased than those in Scr+IS group (all P ＜0.05),and the expression of TIMP1 decreased further (P ＜ 0.05).Conclusions IS can promote the expression of miRNA-21 in myocardial fibroblasts.MiRNA-21 plays an important role in regulating inflammatory factors and pro-fibrogenic cytokines in myocardial fibroblasts.
ABSTRACT
Objective To investigate the clinical and pathological characteristics of IgA nephropathy (IgAN) in association with active tubular interstitial lesions. Methods 148 patients who were diagnosed as IgAN by renal biopsy and admitted to Zhejiang Provincial People's Hospital from March 2014 to December 2014 were enrolled. They were divided into IgAN with active tubular interstitial lesions group (IgAN?ATIL group, 23 patients) and IgAN without active tubular interstitial lesions group (control group, 125 patients). Clinical and pathological characteristics were retrospectively analyzed. Multivariate logistic regression analysis was used to analyze the influence factors. Results The prevalence of ATIL in 148 IgAN patients was 15.5%. IgAN?ATIL group showed an older average age and more higher proportion of medication history (antibiotics, diuretics, nonsteroidal anti ?inflammatory drugs, etc) than those in control group. There were significant differences in Alb, eGFR, Scr, BUN, 24?hour urinary protein quantity, urinary NGAL and urinary RBC count between two groups (P<0.05, respectively). A moderate of tubulointerstitial lesions of IgAN?ATIL group was shown, while the control group was mainly mild lesions. Multivariate logistic regression analysis showed that age, medication history and the urinary NGAL level were independent risk factors of IgAN ? ATIL. Conclusions IgAN patients with active tubular interstitial lesions had more severe clinical manifestations and chronic interstitial lesions. The age, medication history (antibiotics, diuretics, nonsteroidal anti?inflammatory drugs, etc) and the urinary NGAL level were independent risk factors of IgAN?ATIL.