Diabetic nephropathy execrates epithelial-to-mesenchymal transition (EMT) via miR-2467-3p/Twist1 pathway

Xu, Yan; Chen, Ouyang; Lyu, Dayin; Lin, Zhangmei; Zheng, Wen-Cai; Xiao, Fan; Xu, Zhimin; Ding, Lexi

doi:10.1016/j.biopha.2020.109920

Cited by 19 publications

(16 citation statements)

References 28 publications

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“…Epithelial‐to‐mesenchymal transition (EMT), an evolutionarily conserved biologic process through which epithelial cells are transdifferentiated into motile mesenchymal cells, is involved in the progression of fibrosis during diabetic nephropathy 25 . To investigate the effect of mefunidone on EMT in diabetic nephropathy, NRK52E cells were cultured in medium with high glucose for 48 hours to mimic the hyperglycemic condition in vitro.…”

Section: Resultsmentioning

confidence: 99%

“…For T2D, the blood glucose level and urinary albumin level of db/m and db/db mice (n = 6, randomly selected) were measured at the beginning of the study. All animals at eight weeks of age were randomly divided into the following five groups (n = 6 per group): db/m group, db/db model group and MFD-treated diabetic groups (25,50, 100 mg/kg/day). Mefunidone was dissolved in saline solution, and administered daily by gavage to diabetic mice from week 8 to week 24.…”

Section: Animals and Experiments Protocolmentioning

confidence: 99%

“…cells are transdifferentiated into motile mesenchymal cells, is involved in the progression of fibrosis during diabetic nephropathy. 25 To investigate the effect of mefunidone on EMT in diabetic nephropathy, NRK52E cells were cultured in medium with high glucose for 48 hours to mimic the hyperglycemic condition in vitro. Compared with the NG group, the expression of mesenchymal marker α-SMA and transcription factor snail1 significantly elevated and the epithelial marker ZO-1 obviously decreased.…”

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confidence: 99%

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Mefunidone ameliorates diabetic kidney disease in STZ and db/db mice

Jiang

Xie

et al. 2020

FASEB j.

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Diabetic kidney disease (DKD) a kind of microvascular complication, is a primary cause of end-stage renal disease (ESRD) worldwide. 1,2 Characteristic pathological features of DKD include glomerular basement membrane (GBM) thickening, mesangial expansion, glomerulosclerosis, and tubulointerstitial fibrosis, owing to high expression of extracellular matrix (ECM), such as collagen, fibronectin, and so on. 3,4 Type 1 diabetes millitus (T1D) and type 2 diabetes millitus (T2D) are the most common cause of DKD. The incidence of DKD complicated by T1D and T2D is about 50%

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Section: Resultsmentioning

confidence: 99%

Section: Animals and Experiments Protocolmentioning

confidence: 99%

mentioning

confidence: 99%

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Mefunidone ameliorates diabetic kidney disease in STZ and db/db mice

Jiang

Xie

et al. 2020

FASEB j.

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“…EMT is an evolutionarily conserved process in which epithelial cells lose contact adhesion, and acquire some mesenchymal features of migration and production of ECM (Y. Xu et al, 2020). Snail is a transcription factor which could repress the expression of E-cadherin, and induce the expression of mesenchymal proteins such as vimentin, α-SMA and metalloproteinases (Wang et al, 2013;Wang et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Mefunidone Ameliorates Bleomycin-Induced Pulmonary Fibrosis in Mice

Han

Jiang

et al. 2021

Front. Pharmacol.

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Idiopathic pulmonary fibrosis (IPF) is one of the most common and devastating interstitial lung diseases with poor prognosis. Currently, few effective drugs are available for IPF. Hence, we sought to explore the role of mefunidone (MFD), a newly synthesized drug developed by our team, in lung fibrosis. In this study, MFD was found to attenuate bleomycin (BLM) -induced lung fibrosis and inflammation in mice according to Ashcroft and alveolitis scoring. The protein contents and total cell counts in bronchoalveolar lavage fluids of BLM-treated mice were also lowered by MFD. Moreover, the elevation of TGF-β/Smad2 and phosphorylation of MAPK pathways was repressed by MFD. Additionally, MFD attenuated the swelling and vacuolization of mitochondria, lowered the ratio of apoptotic cells, restored the mitochondrial membrane potential, and reversed the expression of cleaved-caspase 3, Bcl-2 and Bax. Meanwhile, the level of epithelial marker, E-cadherin, was restored by MFD, while the levels of mesenchymal markers such as Snail and vimentin were down-regulated by MFD. Besides, MFD inhibited the expression of fibronectin and α-smooth muscle actin in TGF-β treated normal human lung fibroblasts. Thus, our findings suggested that MFD could ameliorate lung fibrosis, cell apoptosis and EMT potentially via suppression of TGF-β/Smad2 and MAPK pathways.

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“…MicroRNAs (miRNAs), as powerful regulators, are involved in the pathogenesis and progression of DN and its complication. Such as miR-135a-5p [ 8 ], miR-451 [ 9 ], miR-770-5p [ 10 ] were elevated, while miR-2467-3p [ 11 ] and miR-30 c-5p [ 12 ] were inhibited in DN. What’s more, As a highly conserved and widely distributed non-coding small RNA molecule (blood, saliva, urine, and tissues), miRNA can be used for early diagnostic detection of diseases.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA (miR)-590-3p alleviates high-glucose induced renal tubular epithelial cell damage by targeting C-X3-C motif chemokine ligand 1 (CX3CL1) in diabetic nephropathy

et al. 2021

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We attempted to analyze the clinical value of microRNA (miR)-590-3p in diabetic nephropathy (DN) patients and its role in high glucose (HG)-induced renal tubular epithelial cell (HK-2) injury. Serum levels of miR-590-3p were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Spearman correlation coefficient analysis of the correlation between miR-590-3p and clinical indicators. The diagnostic value of miR-590-3p was analyzed by the receiver operating characteristic (ROC) curve. Then, the DN cell model induced by HG in HK-2 cells was established. Enzyme-linked immunosorbent assay (ELISA), flow cytometry, and CCK-8 assay were employed to assess cell inflammation, oxidative stress, apoptosis, and proliferation. Dual-luciferase reporter assay confirmed the target of miR-590-3p. Serum miR-590-3p was reduced in patients of DN, which was positively correlated with eGFR and negatively associated with albuminuria. Furthermore, miR-590-3p also can diagnose patients of DN from healthy subjects or patients of T2DM. Furthermore, miR-590-3p was decreased in a concentration- and time-dependent manner during HG-induction. miR-590-3p overexpression bated HG-induced inhibition effect on cell proliferation and promotion effects on apoptosis, oxidative stress, and inflammation. C-X3-C motif chemokine ligand1 (CX3CL1) is the target of miR-590-3p, whose levels were enhanced in DN patients and are negatively regulated by miR-590-3p. Our discoveries offered new insights that reduced miR-590-3p as a potential biomarker for the diagnosis of DN, and elevated miR-590-3p can alleviate renal tubular injury by HG-induced through targeting CX3XL1, which may be a novel target for improving the development of DN.

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Diabetic nephropathy execrates epithelial-to-mesenchymal transition (EMT) via miR-2467-3p/Twist1 pathway

Cited by 19 publications

References 28 publications

Mefunidone ameliorates diabetic kidney disease in STZ and db/db mice

Mefunidone ameliorates diabetic kidney disease in STZ and db/db mice

Mefunidone Ameliorates Bleomycin-Induced Pulmonary Fibrosis in Mice

MicroRNA (miR)-590-3p alleviates high-glucose induced renal tubular epithelial cell damage by targeting C-X3-C motif chemokine ligand 1 (CX3CL1) in diabetic nephropathy

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