MicroRNA-27a promotes podocyte injury via PPARγ-mediated β-catenin activation in diabetic nephropathy

Zhou, Zicong; Wan, Jieqing; Hou, Xiaoyan; Geng, Jiao; Xiao, Li; Bai, Xiaoyan

doi:10.1038/cddis.2017.74

Cited by 90 publications

(71 citation statements)

References 52 publications

(60 reference statements)

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“…MicroRNAs have been demonstrated to be associated with multiple cytological processes of DN, including cell proliferation and apoptosis. [22][23][24] In this study, our results indicated that the expression of miR-15b-5p was significantly decreased following treatment with HG in HK-2 cells. Similarly, Li et al found that miR-25 was markedly decreased in patients with DN, and miR-25 was decreased by HG treatment in HK-2 cells.…”

Section: Discussionsupporting

confidence: 55%

High Glucose-Induced Apoptosis in Human Kidney Cells Was Alleviated by miR-15b-5p Mimics

Shen¹,

Fang²,

Guo³

et al. 2019

Biological & Pharmaceutical Bulletin

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MicroRNAs were involved in a wide range of biological processes of diabetic nephropathy (DN). It is reported that miR-15b-5p was downregulated in the patients with DN. However, the mechanisms underlying the regulatory effects of miR-15b-5p on patients with diabetes remain unclear. Thus, this study aimed to investigate the role of miR-15b-5p during high glucose (HG)-induced apoptosis in human kidney cells. Quantitative real-time (qRT)-PCR was used to detect the level of miR-15b-5p. CCK-8 assay, EdU staining assays and flow cytometry were used to detect cell proliferation, apoptosis respectively in vitro. In addition, Western blotting was used to determine active caspase-3, cleaved poly(ADP-ribose) polymerase (PARP), phosphorylated (p)-AKT, p-mammalian target of rapamycin (mTOR), p-S6, p-c-Jun N terminal kinase (JNK), p-p38 and p-extracellular signal-regulated kinase (ERK) proteins levels. The expression of miR-15b-5p in patients with DN were dramatically decreased compared with health persons. Similarly, HG down-regulated the expression of miR-15b-5p in HK-2 cells. In contrast, miR-15b-5p mimics alleviated HG-induced apoptosis in HK-2 cells via decreasing the expressions of active caspase 3 and cleaved PARP. EdU detection further confirmed that miR-15b-5p mimics attenuated the anti-proliferation effect of HG in HK-2 cells. Furthermore, HGinduced Akt/mTOR pathway downregulation and JNK upregulation were markedly reversed by miR-15b-5p mimics in cells. The data suggested that miR-15b-5p mimics protects HK-2 cells from HG-induced apoptosis. The anti-apoptotic effects of miR-15b-5p may due to the activation of the Akt/mTOR pathway as well as inactivation of JNK. Taken together, miR-15b-5p might be a potential therapeutic target for the treatment of patients with DN.

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Section: Discussionsupporting

confidence: 55%

High Glucose-Induced Apoptosis in Human Kidney Cells Was Alleviated by miR-15b-5p Mimics

Shen¹,

Fang²,

Guo³

et al. 2019

Biological & Pharmaceutical Bulletin

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“…Recently there are several reports that describe the regulatory role of microRNAs in the diabetic nephropathy [49][50][51][52][53][54][55][56][57][58]. We sought to evaluate the miRNA status in the diabetic nephropathy and to assess the physiological relevance with respect to ACE inhibition in diabetic mice.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Angiotensin-Converting Enzyme Ameliorates Renal Fibrosis by Mitigating DPP-4 Level and Restoring Antifibrotic MicroRNAs

Srivastava

Goodwin

Kanasaki

et al. 2020

Genes

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Two class of drugs 1) angiotensin-converting enzyme inhibitors (ACEis) and 2) angiotensin II receptor blockers (ARBs) are well-known conventional drugs that can retard the progression of chronic nephropathies to end-stage renal disease. However, there is a lack of comparative studies on the effects of ACEi versus ARB on renal fibrosis. Here, we observed that ACEi ameliorated renal fibrosis by mitigating DPP-4 and TGFβ signaling, whereas, ARB did not show. Moreover, the combination of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP), one of the substrates of ACE, with ACEi slightly enhanced the inhibitory effects of ACEi on DPP-4 and associated-TGFβ signaling. Further, the comprehensive miRome analysis in kidneys of ACEi+AcSDKP (combination) treatment revealed the emergence of miR-29s and miR-let-7s as key antifibrotic players. Treatment of cultured cells with ACEi alone or in combination with AcSDKP prevented the downregulated expression of miR-29s and miR-let-7s induced by TGFβ stimulation. Interestingly, ACEi also restored miR-29 and miR-let-7 family cross-talk in endothelial cells, an effect that is shared by AcSDKP suggesting that AcSDKP may be partially involved in the anti-mesenchymal action of ACEi. The results of the present study promise to advance our understanding of how ACEi regulates antifibrotic microRNAs crosstalk and DPP-4 associated-fibrogenic processes which is a critical event in the development of diabetic kidney disease.

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“…And, micro-RNA23 can be mediated by PPARc in renal calcium oxalate crystal formation. lncRNA TUG1 could modulate ECM accumulation in DN by regulating miR-377 targeting PPARc [48][49][50]. However, the role of the epigenetic modification in PPARc function in kidney diseases still needs further exploration.…”

Section: Pparγ and Kidney Fibrosismentioning

confidence: 99%

PPARγ and Its Agonists in Chronic Kidney Disease

Shi

Wang

et al. 2020

International Journal of Nephrology

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Chronic kidney disease (CKD) has become a global healthcare issue. CKD can progress to irreversible end-stage renal diseases (ESRD) or renal failure. e major risk factors for CKD include obesity, diabetes, and cardiovascular diseases. Understanding the key process involved in the disease development may lead to novel interventive strategies, which is currently lagging behind. Peroxisome proliferator-activated receptor c (PPARc) is one of the ligand-activated transcription factor superfamily members and is globally expressed in human tissues. Its agonists such as thiazolidinediones (TZDs) have been applied as effective antidiabetic drugs as they control insulin sensitivity in multiple metabolic tissues. Besides, TZDs exert protective effects in multiple other CKD risk disease contexts. As PPARc is abundantly expressed in major kidney cells, its physiological roles in those cells have been studied in both cell and animal models. e function of PPARc in the kidney ranges from energy metabolism, cell proliferation to inflammatory suppression, although major renal side effects of existing agonists (including TZDs) have been reported, which limited their application in treating CKD. In the current review, we systemically assess the function of PPARc in CKDs and the benefits and current limitations of its agonists in the clinical applications.

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MicroRNA-27a promotes podocyte injury via PPARγ-mediated β-catenin activation in diabetic nephropathy

Cited by 90 publications

References 52 publications

High Glucose-Induced Apoptosis in Human Kidney Cells Was Alleviated by miR-15b-5p Mimics

High Glucose-Induced Apoptosis in Human Kidney Cells Was Alleviated by miR-15b-5p Mimics

Inhibition of Angiotensin-Converting Enzyme Ameliorates Renal Fibrosis by Mitigating DPP-4 Level and Restoring Antifibrotic MicroRNAs

PPARγ and Its Agonists in Chronic Kidney Disease

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