BMP-7 inhibits renal fibrosis in diabetic nephropathy via miR-21 downregulation

Liu, Lingling; Wang, Yuanyuan; Yan, Rui; Liang, Luqun; Zhou, Xingcheng; Liu, Huiming; Zhang, Xiaohuan; Mao, Yanwen; Wei, Peng; Xiao, Ying; Zhang, Fan; Liu, Lirong; Shi, Mingjun; Guo, Bing

doi:10.1016/j.lfs.2019.116957

Cited by 71 publications

(48 citation statements)

References 30 publications

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“…The copy number is calculated by transforming the Ct values, which is exponential by nature, into linear arithmetic values. miR-21 has been associated with renal fibrosis [36][37][38]. It was also found that miR-21 increased with the disease (IgAN) severity in previous studies carried on serum, urine, kidney tissues and it was able to differentiate the segmental sclerosis (S) stages [39][40][41].…”

Section: Discussionmentioning

confidence: 97%

Mean Expression Value Normalized and Absolute Quantified miR-21 Found to be a Potential Diagnostic and Prognostic Marker for IgA Nephropathy

Kumar¹

2020

IJST

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Background/objectives: miR-21 has been linked to renal fibrosis and miR-155 too has shown different expression in IgAN whose pathogenesis is partially understood. In this study, we explored the utility of miR-21 and miR-155 in IgA nephropathy. Methods: We recruited 40 IgA nephropathy (IgAN) patients and 15 healthy controls (HC). 2 ml blood sample was collected from each study participant. Mean expressed value normalization and absolute and relative quantification methods were used for quantitative polymerase chain reaction (PCR) experiment for miRNA expression. Logistic regression analysis was performed for diagnostic and prognostic value of miR-21. Findings: Mean expressed value normalization reduced the variation in groups and between groups without changing the mean value. miR-155 showed similar expression in IgAN and healthy controls. There was threefold increases in miR-21 in IgAN than the HC. miR-21 was able to differentiate the mesangial hypercellularity and tubular atrophy/interstitial fibrosis stages with sensitivity 84 and 70 percent, respectively. Applications: miR-155 can be used as a reference control gene for IgAN on quantitative PCR-based experiments. miR-21 can be used as a diagnostic and prognostic marker for IgAN.

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Section: Discussionmentioning

confidence: 97%

Mean Expression Value Normalized and Absolute Quantified miR-21 Found to be a Potential Diagnostic and Prognostic Marker for IgA Nephropathy

Kumar¹

2020

IJST

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“…Furthermore, miR-21 antagonism in a STZinduced diabetic mouse model resulted in reduced fibrotic and inflammatory gene expression, as well as reduced mesangial expansion, podocyte loss, interstitial fibrosis, macrophage infiltration, and proteinuria (Kolling et al, 2017). Liu et al (2019) reported that bone morphogenetic protein 7 (BMP-7), a human recombinant protein, inhibited EMT and ECM synthesis and accumulation in rat renal tubular epithelial (NRK-52E) cells cultured under high glucose conditions. Moreover, injection of a BMP-7-overexpressing plasmid to STZ-diabetic mice caused a significant decrease in miR-21 expression and upregulated Smad7 expression, thereby leading to the prevention of EMT and ECM accumulation.…”

Section: Profibrotic Mirna In Diabetic Kidney Disease 【Mir-21】mentioning

confidence: 99%

Potential Targeting of Renal Fibrosis in Diabetic Kidney Disease Using MicroRNAs

et al. 2020

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Diabetic kidney disease (DKD) is a major health problem and one of the leading causes of end-stage renal disease worldwide. Despite recent advances, there exists an urgent need for the development of new treatments for DKD. DKD is characterized by the excessive synthesis and deposition of extracellular matrix proteins in glomeruli and the tubulointerstitium, ultimately leading to glomerulosclerosis as well as interstitial fibrosis. Renal fibrosis is the final common pathway at the histological level leading to an end-stage renal failure. In fact, activation of the nuclear factor erythroid 2-related factor 2 pathway by bardoxolone methyl and inhibition of transforming growth factor beta signaling by pirfenidone have been assumed to be effective therapeutic targets for DKD, and various basic and clinical studies are currently ongoing. MicroRNAs (miRNAs) are endogenously produced small RNA molecules of 18–22 nucleotides in length, which act as posttranscriptional repressors of gene expression. Studies have demonstrated that several miRNAs contribute to renal fibrosis. In this review, we outline the potential of using miRNAs as an antifibrosis treatment strategy and discuss their clinical application in DKD.

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“…Although the underlying mechanism was not classified, it was shown that these two miR-NAs could activate the expression levels of TGF-β1 and NF-κB in renal tissue of diabetic patients and animal models [60]. Furthermore, miR-21 was also increased under the condition of hyperglycemia and targeted to the expression of TSP-1 [61] which was linked to activation of TGF-β1/Smad7 signaling [62]. In contrast, other miR-NAs were reduced in diabetic conditions, such as miR-30c, miR-23, and miR-29 [63].…”

Section: Endoplasmic Reticulum (Er)mentioning

confidence: 99%

“…Second, miRNAs are involved in increasing the expression of TSP-1. For instance, deregulation of miR-320c, miR-21, and miR-192 which has an effect on TGF-β1 and TSP-1 attenuated the progression of DN [62,63,66]. Finally, suppression of ER stress could prevent the progression of fibrosis in DN [102], which might be associated with inhibiting the expression of TSP-1 [48].…”

Section: 1mentioning

confidence: 99%

Thrombospondin-1: A Key Protein That Induces Fibrosis in Diabetic Complications

Zhang

Chen

et al. 2020

Journal of Diabetes Research

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Fibrosis accompanies most common pathophysiological features of diabetes complications in different organs. It is characterized by an excessive accumulation of extracellular matrix (ECM) components, the response to which contributes to inevitable organ injury. The extracellular protein thrombospondin-1 (TSP-1), a kind of extracellular glycoprotein, is upregulated by the increased activity of some transcription factors and results in fibrosis by activating multiple pathways in diabetes. The results of studies from our team and other colleagues indicate that TSP-1 is associated with the pathological process leading to diabetic complications and is considered to be the most important factor in fibrosis. This review summarizes the molecular mechanism of increased TSP-1 induced by hyperglycemia and the role of TSP-1 in fibrosis during the development of diabetes complications.

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BMP-7 inhibits renal fibrosis in diabetic nephropathy via miR-21 downregulation

Cited by 71 publications

References 30 publications

Mean Expression Value Normalized and Absolute Quantified miR-21 Found to be a Potential Diagnostic and Prognostic Marker for IgA Nephropathy

Mean Expression Value Normalized and Absolute Quantified miR-21 Found to be a Potential Diagnostic and Prognostic Marker for IgA Nephropathy

Potential Targeting of Renal Fibrosis in Diabetic Kidney Disease Using MicroRNAs

Thrombospondin-1: A Key Protein That Induces Fibrosis in Diabetic Complications

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