scholarly journals Astragaloside IV inhibits excessive mesangial cell proliferation and renal fibrosis caused by diabetic nephropathy via modulation of the TGF‑β1/Smad/miR‑192 signaling pathway

2019 ◽  
Author(s):  
Qian Mao ◽  
Cuicui Chen ◽  
Huankun Liang ◽  
Shuhai Zhong ◽  
Xinbo Cheng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Renal Fibrosis ◽  
Mesangial Cell ◽  
Astragaloside Iv ◽  
Mesangial Cell Proliferation ◽  
Tgf Β1

scholarly journals Ergosterol Ameliorates Diabetic Nephropathy by Attenuating Mesangial Cell Proliferation and Extracellular Matrix Deposition via the TGF-β1/Smad2 Signaling Pathway

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 483 ◽  
Author(s):  
Zhonghua Dong ◽  
Yueyue Sun ◽  
Guangwei Wei ◽  
Siying Li ◽  
Zhongxi Zhao
Keyword(s):  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Diabetic Mice ◽  
Mesangial Cell Proliferation ◽  
Tgf Β1

(1) Background: Diabetic nephropathy, a microvascular complication of diabetes, is one of the principal causes of end-stage renal disease worldwide. The aim of this study was to explore the therapeutic effects of ergosterol on diabetic nephropathy. (2) Methods: Streptozotocin (STZ)-induced C57BL/6 diabetic mice were treated with ergosterol (10, 20, 40 mg/kg/day) for 8 weeks by oral gavage. The in vitro study employed rat mesangial cells exposed to 30 mM glucose for 48 h in the presence of 10 or 20 μM ergosterol. (3) Results: Ergosterol treatment improved body weights, ameliorated the majority of biochemical and renal functional parameters and histopathological changes, and reduced extracellular matrix (ECM) deposition in diabetic mice. In vitro, ergosterol suppressed proliferation, reduced the levels of ECM proteins, and increased the expression of matrix metalloproteinase-2 and -9 in high glucose-induced mesangial cells; Furthermore, ergosterol markedly improved transforming growth factor-β1 (TGF-β1) expression, enhanced phosphorylation levels of drosophila mothers against decapentaplegic 2 (Smad2), and regulated the downstream factors in vivo and in vitro. (4) Conclusions: Ergosterol alleviated mesangial cell proliferation and the subsequent ECM deposition by regulating the TGF-β1/Smad2 signaling pathway.

The role of the BMP4/Smad1 signaling pathway in mesangial cell proliferation: A possible mechanism of diabetic nephropathy

Life Sciences ◽  
2019 ◽  
Vol 220 ◽  
pp. 106-116 ◽  
Author(s):  
Cheng Chen ◽  
Jiaru Lin ◽  
Li Li ◽  
Tingting Zhu ◽  
Lichao Gao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Mesangial Cell ◽  
Mesangial Cell Proliferation

scholarly journals Sauchinone Protects Renal Mesangial Cell Dysfunction against Angiotensin II by Improving Renal Fibrosis and Inflammation

2020 ◽  
Vol 21 (19) ◽  
pp. 7003
Author(s):  
Jung Joo Yoon ◽  
Hyeon Kyoung Lee ◽  
Hye Yoom Kim ◽  
Byung Hyuk Han ◽  
Ho Sub Lee ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Diabetic Nephropathy ◽  
Angiotensin Ii ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Tissue Growth ◽  
Biologically Active ◽  
Dependent Manner ◽  
Saururus Chinensis ◽  
Mesangial Cell Proliferation

Abnormal and excessive growth of mesangial cells is important in the pathophysiologic processes of diabetes-associated interstitial fibrosis and glomerulosclerosis, leading to diabetic nephropathy, which eventually turns into end-stage renal disease. Sauchinone, a biologically-active lignan isolated from aerial parts of Saururus chinensis, has anti-inflammatory and anti-viral activities effects on various cell types. However, there are no studies reporting the effects of sauchinone on diabetic nephropathy. The present study aims to investigate the role of sauchinone in mesangial cell proliferation and fibrosis induced by angiotensin II, as well as the underlying mechanisms of these processes. Human renal mesangial cells were induced by angiotensin II (AngII, 10 μM) in the presence or absence of sauchinone (0.1–1 μM) and incubated for 48 h. In this study, we found that AngII induced mesangial cell proliferation, while treatment with sauchinone inhibited the cell proliferation in a dose-dependent manner. Pre-treatment with sauchinone induced down-regulation of cyclins/CDKs and up-regulation of CDK inhibitor, p21, and p27kip1 expression. In addition, AngII-enhanced expression of fibrosis biomarkers such as fibronectin, collagen IV, and connective tissue growth factor (CTGF), which was markedly attenuated by sauchinone. Sauchinone also decreased AngII-induced TGF-β1 and Smad-2, Smad-3, and Smad-4 expression. This study further revealed that sauchinone ameliorated AngII-induced mesangial inflammation through disturbing activation of inflammatory factors, and NLRP3 inflammasome, which is composed of the NLRP3 protein, procaspase-1, and apoptosis-associated speck-like protein containing a CARD (ASC). Moreover, pretreatment of sauchinone inhibited NF-κB translocation and ROS production in AngII-exposed mesangial cells. These data suggest that sauchinone has a protective effect on renal proliferation, fibrosis and inflammation. Therefore, sauchinone might be a potential pharmacological agent in prevention of AngII-induced renal damage leading to diabetic nephropathy.

scholarly journals Smooth-Muscle Calponin in Mesangial Cells: Regulation of Expression and a Role in Suppressing Glomerulonephritis

2002 ◽  
Vol 13 (2) ◽  
pp. 322-331 ◽  
Author(s):  
Youichi Sugenoya ◽  
Ashio Yoshimura ◽  
Hisako Yamamura ◽  
Kiyoko Inui ◽  
Hiroyuki Morita ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Actin Binding ◽  
Luciferase Reporter ◽  
Tnf Α ◽  
Mesangial Cell Proliferation ◽  
Tgf Β1

ABSTRACT. The basic or h1 calponin gene, which encodes an actin-binding protein involved in the regulation of smooth-muscle shortening velocity, is known to be a smooth-muscle differentiation-specific gene. It was found that basic calponin was expressed by cultured mesangial cells and localized along the actin filaments. Among the growth factors involved in the mesangial cell pathophysiology, including platelet-derived growth factor-BB (PDGF-BB), tumor necrosis factor–α (TNF-α), and transforming growth factor–β1 (TGF-β1), TNF-α potently downregulates basic calponin expression in both the mRNA and protein levels, whereas TGF-β1 upregulates the calponin expression. PDGF-BB also reduced its mRNA expression. The half-life of basic calponin mRNA was determined to be similar between TNF-α–treated and –untreated mesangial cells, whereas cell transfection assays that used a luciferase reporter gene construct containing the functional basic calponin promoter showed that TNF-α and PDGF-BB reduced the transcriptional activity. Because stimulation with TNF-α and PDGF-BB was associated with mesangial cell proliferation, basic calponin may play a role in the suppression of mesangial cell proliferation. Treatment with anti–glomerular basement membrane antibody in calponin knockout mice induced more severe nephritis than in wild type mice, as judged from an increase in the urinary protein excretion, glomerular cellularity, and number of proliferating cell nuclear antigen–positive cells in glomerulus. These results suggest that basic calponin expression may serve as one of the intrinsic regulators of glomerular nephritis. Elucidation of the molecular mechanisms for regulation of the basic calponin expression in mesangial cells may improve the understanding of the molecular basis and pathogenesis of the glomerular response to injury.

Knock-Down of Long Non-Coding RNA ANRIL Suppresses Mouse Mesangial Cell Proliferation, Fibrosis, Inflammation via Regulating Wnt/β-Catenin and MEK/ERK Pathways in Diabetic Nephropathy

2020 ◽  
Author(s):  
Xun Fang ◽  
Jun Hu ◽  
Hongyan Zhou
Keyword(s):  
Cell Proliferation ◽  
Diabetic Nephropathy ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Necrosis Factor Alpha ◽  
Monocyte Chemoattractant Protein 1 ◽  
Knock Down ◽  
Non Coding Rna ◽  
Mesangial Cell Proliferation ◽  
Long Non Coding Rna

Abstract Aims Our study aimed to investigate the role of long non-coding RNA ANRIL (lnc-ANRIL) knock-down in regulating cell activities, inflammation and downstream signaling pathways in mouse mesangial cellular diabetic nephropathy (DN) model. Methods The mouse mesangial cells (SV40-MES13 cells) were treated with high-glucose (HG) to construct cellular DN model. Lnc-ANRIL knock-down plasmid and control knock-down plasmid were transfected into HG-treated SV40-MES13 cells as Sh-ANRIL group and Sh-NC group respectively. Results Lnc-ANRIL expression was significantly higher in HG-treated SV40-MES13 cells compared with normal glucose-treated SV40-MES13 cells and osmotic control-treated SV40-MES13 cells. Lnc-ANRIL knock-down suppressed cell proliferation and promoted cell apoptosis in HG-treated SV40-MES13 cells. As for fibrosis, lnc-ANRIL knock-down reduced fibronectin and collagen I expressions in HG-treated SV40-MES13 cells. Besides, the expressions of supernatant tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-1β, IL-6, IL-8 and IL-18 were reduced in Sh-ANRIL group compared with Sh-NC group. Furthermore, Wnt3, β-catenin, p-MEK1 and p-ERK1 expressions were suppressed in Sh-ANRIL group compared with Sh-NC group, which suggested that lnc-ANRIL knock-down inhibited Wnt/β-catenin and MEK/ERK pathways in HG-treated SV40-MES13 cells. Conclusions Lnc-ANRIL knock-down suppresses mouse mesangial cell proliferation, fibrosis, inflammation, Wnt/β-catenin and MEK/ERK pathways in DN.

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