Effect of miR-21 on Renal Fibrosis Induced by Nano-SiO2 in Diabetic Nephropathy Rats via PTEN/AKT Pathway

2021 ◽  
Vol 21 (2) ◽  
pp. 1079-1084
Author(s):  
Jifan Guo
Keyword(s):  
Diabetic Nephropathy ◽  
Renal Fibrosis ◽  
Kidney Diseases ◽  
Mrna Translation ◽  
Research Progress ◽  
Akt Pathway ◽  
Pten Gene ◽  
Cell Phenotype ◽  
Pten Protein ◽  
Target Mrna

MicroRNAs are a type of non-coding single-stranded RNA that can mediate target mRNA degradation or inhibit target mRNA translation, thereby regulating target gene expression and have an important role in physiological and pathological processes. At present, miRs have been confirmed to be closely related to kidneys and kidney diseases, and have been involved in the occurrence, development and prognosis of renal fibrosis. Now we review the research progress of miRs in renal fibrosis in recent years, and provide references for the future diagnosis and treatment of renal fibrosis. The incidence of diabetic nephropathy (DN) is increasing year by year, the pathogenesis is complicated, and renal fibrosis occurs during the progress of the disease, which is very difficult to treat. The protein encoded by the PTEN gene has lipid phosphatase and protein phosphatase activity and is the PTEN/AKT and FAK pathway important negative regulators. It can play an anti-fibrotic effect by negatively regulating the PTEN/AKT pathway. Studies show that during the pathogenesis of DN, the expression of PTEN protein is reduced, and the PI3K/AKT pathway is activated to exert multiple fibrotic effects, but affect PTEN. The regulatory factors of expression are still not clear; moreover, the specific mechanism of the decrease in PTEN protein expression in DN pathogenesis. Therefore, this study intends to Intervention of the expression level of miRs in renal tissues, to study its regulation of PTEN and its effect on renal fibrosis, and at the same time, observe the effects on renal tubular epithelial cell phenotype and fibrotic lesions under high glucose conditions by up-regulating and down-regulating PTEN expression. Further elucidate the pathogenesis of DN renal fibrosis, and explore new effective targets for the prevention and treatment of DN.

scholarly journals The Alcohol Extract of Coreopsis tinctoria Nutt Ameliorates Diabetes and Diabetic Nephropathy in db/db Mice through miR-192/miR-200b and PTEN/AKT and ZEB2/ECM Pathways

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Shunjie Yu ◽  
Haoran Zhao ◽  
Wenjing Yang ◽  
Ramila Amat ◽  
Jun Peng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Diabetic Nephropathy ◽  
Renal Fibrosis ◽  
Target Gene ◽  
Urinary Albumin Excretion ◽  
Fasting Blood Glucose ◽  
Urinary Albumin ◽  
Akt Pathway ◽  
Alcohol Extract ◽  
Coreopsis Tinctoria

The study aims to investigate the effects of the alcohol extract of Coreopsis tinctoria Nutt (AC) on diabetic nephropathy (DN) mice. A total of 30 db/db (DN) mice were divided into 3 groups, which were treated with AC (300 mg/kg/day), metformin (180 mg/kg/day), or saline by gavage for 10 weeks. Ten db/m mice treated with saline were used as normal control (NC group). Body weight (BW) and fasting blood glucose (FBG), HbA1c, 24 h urinary albumin excretion (UAE), and renal pathological fibrosis were analyzed. Expression of miR-192, miR-200b, and proteins in the PTEN/PI3K/AKT pathway was analyzed by qPCR or western blot. The DN mice had significantly higher BW, FBG, and 24 h UAE, as well as more severe pathological fibrosis when compared with NC. Treatment of AC could decrease BW, FBG, and 24 h UAE and alleviated kidney damage. Compared with the NC group, expressions of miR-192 and miR-200b were increased, whereas their target proteins (ZEB2 and PTEN) were reduced in the kidneys of DN mice, which further modulated the expression of their downstream proteins PI3K p85α, P-AKT, P-smad3, and COL4 α1; these proteins were increased in the kidneys of DN mice. In contrast, AC treatment reversed the expression changes of these proteins. These findings demonstrate that AC may protect the kidneys of DN mice by decreasing miR-192 and miR-200b, which could further regulate their target gene expression and modulate the activity of the PTEN/PI3K/AKT pathway to reduce the degree of renal fibrosis.

scholarly journals Inhibition of TGF-β1 Signaling by IL-15: A Novel Role for IL-15 in the Control of Renal Epithelial-Mesenchymal Transition: IL-15 Counteracts TGF-β1-Induced EMT in Renal Fibrosis

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Aurore Devocelle ◽  
Lola Lecru ◽  
Hélène François ◽  
Christophe Desterke ◽  
Cindy Gallerne ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Renal Fibrosis ◽  
Epithelial Mesenchymal Transition ◽  
Kidney Diseases ◽  
Mesenchymal Transition ◽  
Matrix Deposition ◽  
Renal Tubulointerstitial Fibrosis ◽  
Tgf Β1

Renal tubulointerstitial fibrosis is the final common pathway in end-stage renal disease and is characterized by aberrant accumulation of extracellular matrix (ECM) components secreted by myofibroblasts. Tubular type 2 EMT, induced by TGF-β, plays an important role in renal fibrosis, by participating directly or indirectly in myofibroblasts generation. TGF-β1-induced apoptosis and fibrosis in experimental chronic murine kidney diseases are concomitantly associated with an intrarenal decreased expression of the IL-15 survival factor. Since IL-15 counteracts TGF-β1 effects in different cell models, we analyzed whether (1) human chronic inflammatory nephropathies evolving towards fibrosis could be also characterized by a weak intrarenal IL-15 expression and (2) IL-15 could inhibit epithelial-mesenchymal transition (EMT) and excess matrix deposition in human renal proximal tubular epithelial cells (RPTEC). Our data show that different human chronic kidney diseases are characterized by a strong decreased expression of intrarenal IL-15, which is particularly relevant in diabetic nephropathy, in which type 2 tubular EMT plays an important role in fibrosis. Moreover, primary epithelial tubular cultures deprived of growth supplements rapidly produce active TGF-β1 inducing a “spontaneous” EMT process characterized by the loss of membrane-bound IL-15 (mbIL-15) expression. Both “spontaneous” EMT and recombinant human (rh) TGF-β1-induced EMT models can be inhibited by treating RPTEC and HK2 cells with rhIL-15. Through a long-lasting phospho-c-jun activation, IL-15 inhibits rhTGF-β1-induced Snail1 expression, the master inducer of EMT, and blocks TGF-β1-induced tubular EMT and downstream collagen synthesis. In conclusion, our data suggest that intrarenal IL-15 could be a natural inhibitor of TGF-β in human kidney able to guarantee epithelial homeostasis and to prevent EMT process. Thus, both in vivo and in vitro an unbalance in intrarenal IL-15 and TGF-β1 levels could render RPTEC cells more prone to undergo EMT process. Exogenous IL-15 treatment could be beneficial in some human nephropathies such as diabetic nephropathy.

scholarly journals Protective Effects of Ethanolic Extract from Rhizome of Polygoni avicularis against Renal Fibrosis and Inflammation in a Diabetic Nephropathy Model

2021 ◽  
Vol 22 (13) ◽  
pp. 7230
Author(s):  
Jung-Joo Yoon ◽  
Ji-Hun Park ◽  
Yun-Jung Lee ◽  
Hye-Yoom Kim ◽  
Byung-Hyuk Han ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Diabetic Nephropathy ◽  
Renal Dysfunction ◽  
Renal Fibrosis ◽  
Mesangial Cells ◽  
Resistance Index ◽  
Ethanolic Extract ◽  
Glomerular Sclerosis ◽  
Oral Glucose ◽  
Inflammatory Factor

Progressive diabetic nephropathy (DN) in diabetes leads to major morbidity and mortality. The major pathological alterations of DN include mesangial expansion, extracellular matrix alterations, tubulointerstitial fibrosis, and glomerular sclerosis. Polygoni avicularis is widely used in traditional oriental medicine and has long been used as a diuretic, astringent, insecticide and antihypertensive. However, to the best of the authors’ knowledge, the effects of the ethanolic extract from rhizome of Polygoni avicularis (ER-PA) on DN have not yet been assessed. The present study aimed to identify the effect of ER-PA on renal dysfunction, which has been implicated in DN in human renal mesangial cells and db/db mice and investigate its mechanism of action. The in vivo experiment was performed using Polygoni avicularis-ethanol soluble fraction (ER-PA) and was administrated to db/db mice at 10 and 50 mg/kg dose. For the in vitro experiments, the human renal mesangial cells were induced by high glucose (HG, 25 mM). The ER-PA group showed significant amelioration in oral glucose tolerance, and insulin resistance index. ER-PA significantly improved the albumin excretion and markedly reduced plasma creatinine, kidney injury molecule-1 and C-reactive protein. In addition, ER-PA significantly suppressed inflammatory cytokines. Histopathologically, ER-PA attenuated glomerular expansion and tubular fibrosis in db/db mice. Furthermore, ER-PA suppressed the expression of renal fibrosis biomarkers (TGF and Collagen IV). ER-PA also reduced the NLR family pyrin domain containing 3 inflammatory factor level. These results suggest that ER-PA has a protective effect against renal dysfunction through improved insulin resistance as well as the inhibition of nephritis and fibrosis in DN.

Fate alteration of bone marrow-derived macrophages ameliorates kidney fibrosis in murine model of unilateral ureteral obstruction

2018 ◽  
Vol 34 (10) ◽  
pp. 1657-1668 ◽  
Author(s):  
Ying Yang ◽  
Xiaojian Feng ◽  
Xinyan Liu ◽  
Ying Wang ◽  
Min Hu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Kidney Diseases ◽  
Unilateral Ureteral Obstruction ◽  
Immunofluorescent Staining ◽  
Enzyme Linked Immunosorbent Assay ◽  
Pathological Feature ◽  
Kidney Fibrosis ◽  
Anti Inflammatory

AbstractBackgroundRenal fibrosis is a key pathological feature and final common pathway leading to end-stage kidney failure in many chronic kidney diseases. Myofibroblast is the master player in renal fibrosis. However, myofibroblasts are heterogeneous. Recent studies show that bone marrow-derived macrophages transform into myofibroblasts by transforming growth factor (TGF)-β-induced macrophage–myofibroblast transition (MMT) in renal fibrosis.MethodsTGF-β signaling was redirected by inhibition of β-catenin/T-cell factor (TCF) to increase β-catenin/Foxo in bone marrow-derived macrophages. A kidney fibrosis model of unilateral ureteral obstruction was performed in EGFP bone marrow chimera mouse. MMT was examined by flow cytometry analysis of GFP+F4/80+α-SMA+ cells from unilateral ureteral obstruction (UUO) kidney, and by immunofluorescent staining of bone marrow-derived macrophages in vitro. Inflammatory and anti-inflammatory cytokines were analysis by enzyme-linked immunosorbent assay.ResultsInhibition of β-catenin/TCF by ICG-001 combined with TGF-β1 treatment increased β-catenin/Foxo1, reduced the MMT and inflammatory cytokine production by bone marrow-derived macrophages, and thereby, reduced kidney fibrosis in the UUO model.ConclusionsOur results demonstrate that diversion of β-catenin from TCF to Foxo1-mediated transcription not only inhibits the β-catenin/TCF-mediated fibrotic effect of TGF-β, but also enhances its anti-inflammatory action, allowing therapeutic use of TGF-β to reduce both inflammation and fibrosis at least partially by changing the fate of bone marrow-derived macrophages.

scholarly journals Glucagon-Like Peptide-1 Mediates the Protective Effect of the Dipeptidyl Peptidase IV Inhibitor on Renal Fibrosis via Reducing the Phenotypic Conversion of Renal Microvascular Cells in Monocrotaline-Treated Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Jian Xu ◽  
Jingjing Wang ◽  
Yusheng Cheng ◽  
Xiang Li ◽  
Mengyu He ◽  
...  
Keyword(s):  
Protective Effect ◽  
Renal Fibrosis ◽  
Kidney Diseases ◽  
Dipeptidyl Peptidase ◽  
Dependent Manner ◽  
Mesenchymal Transition ◽  
Matrix Deposition ◽  
Renal Microcirculation ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Chronic kidney diseases are characterized by renal fibrosis with excessive matrix deposition, leading to a progressive loss of functional renal parenchyma and, eventually, renal failure. Renal microcirculation lesions, including the phenotypic conversion of vascular cells, contribute to renal fibrosis. Here, renal microcirculation lesions were established with monocrotaline (MCT, 60 mg/kg). Sitagliptin (40 mg/kg/d), a classical dipeptidyl peptidase-4 (DPP-4) inhibitor, attenuated the renal microcirculation lesions by inhibiting glomerular tuft hypertrophy, glomerular mesangial expansion, and microvascular thrombosis. These effects of sitagliptin were mediated by glucagon-like peptide-1 receptor (GLP-1R), since they were blocked by the GLP-1R antagonist exendin-3 (Ex-3, 40 ug/kg/d). The GLP-1R agonist liraglutide showed a similar renal protective effect in a dose-independent manner. In addition, sitagliptin, as well as liraglutide, alleviated the MCT-induced apoptosis of renal cells by increasing the expression of survival factor glucose-regulated protein 78 (GRP78), which was abolished by the GLP-1R antagonist Ex-3. Sitagliptin and liraglutide also effectively ameliorated the conversion of vascular smooth muscle cells (SMCs) from a synthetic phenotype to contractile phenotype. Moreover, sitagliptin and liraglutide inhibited endothelial-mesenchymal transition (EndMT) via downregulating transforming growth factor-β1 (TGF-β1). Collectively, these findings suggest that DPP-4 inhibition can reduce microcirculation lesion-induced renal fibrosis in a GLP-1-dependent manner.

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