High glucose promotes hepatic fibrosis via miR‑32/MTA3‑mediated epithelial‑to‑mesenchymal transition

Li, Qiang; Li, Zhange; Yuan, Lin; Che, Hui; Hu, Yingying; Kang, Xujuan; Zhang, Ying; Wang, Lihong; Zhang, Yong

doi:10.3892/mmr.2019.9986

Cited by 8 publications

(9 citation statements)

References 44 publications

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“…As the main components of ECM, Col‐I and Col‐III are enhanced in fibrotic liver. The protein and mRNA expression of Col‐I increase in hyperglycemia‐induced hepatic fibrosis in rats . Carbon tetrachloride (CCl 4 ) can accumulate a significant amount of Col‐III in mouse liver .…”

Section: Discussionmentioning

confidence: 99%

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TGF‐β1 mediated Smad signaling pathway and EMT in hepatic fibrosis induced by Nano NiO in vivo and in vitro

Zhang

Chang

Wang

et al. 2019

Environmental Toxicology

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Nickel oxide nanoparticles (Nano NiO) bears hepatotoxicity, while whether it leads to liver fibrosis remains unclear. The aim of this study was to establish the Nano NiO‐induced hepatic fibrosis model in vivo and investigate the roles of transforming growth factor β1 (TGF‐β1) in Smad pathway activation, epithelial‐mesenchymal transition (EMT) occurrence, and extracellular matrix (ECM) deposition in vitro. Male Wistar rats were exposed to 0.015, 0.06, and 0.24 mg/kg Nano NiO by intratracheal instilling twice a week for 9 weeks. HepG2 cells were treated with 100 μg/mL Nano NiO and TGF‐β1 inhibitor (SB431542) to explore the mechanism of collagen formation. Results of Masson staining as well as the elevated levels of type I collagen (Col‐I) and Col‐III suggested that Nano NiO resulted in hepatic fibrosis in rats. Furthermore, Nano NiO increased the protein expression of TGF‐β1, p‐Smad2, p‐Smad3, alpha‐smooth muscle actin (α‐SMA), matrix metalloproteinase9 (MMP9), and tissue inhibitors of metalloproteinase1 (TIMP1), while decreased the protein content of E‐cadherin and Smad7 in rat liver and HepG2 cells. Most importantly, Nano NiO‐triggered the abnormal expression of the abovementioned proteins were all alleviated by co‐treatment with SB431542, implying that TGF‐β1‐mediated Smad pathway, EMT and MMP9/TIMP1 imbalance were involved in overproduction of collagen in HepG2 cells. In conclusion, these findings indicated that Nano NiO induced hepatic fibrosis via TGF‐β1‐mediated Smad pathway activation, EMT occurrence, and ECM deposition.

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Section: Discussionmentioning

confidence: 99%

“…16 The protein and mRNA expression of Col-I increase in hyperglycemia-induced hepatic fibrosis in rats. 42 Carbon tetrachloride (CCl 4 ) can accumulate a significant amount of Col-III in mouse liver. 43 Increasing expressions of Col-I and Col-III are related to hepatic fibrosis 44 and bile duct ligation.…”

Section: Nano Nio Induced Hepatic Fibrosis In Ratsmentioning

confidence: 99%

TGF‐β1 mediated Smad signaling pathway and EMT in hepatic fibrosis induced by Nano NiO in vivo and in vitro

Zhang

Chang

Wang

et al. 2019

Environmental Toxicology

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“…Cell viability was detected with Cell Counting Kit-8 (CCK-8; Dojindo, Kumamoto, Japan) as previously described by our laboratory 24 . Briefly, neonatal cardiomyocytes (60% confluence) were cultured in 96-well plates followed by constructive transfection or hypoxia treatment.…”

Section: Methodsmentioning

confidence: 99%

GDF11 inhibits cardiomyocyte pyroptosis and exerts cardioprotection in acute myocardial infarction mice by upregulation of transcription factor HOXA3

Li¹,

Xu²,

Liu³

et al. 2020

Cell Death Dis

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NLRP3 (Nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3) inflammasome-mediated cardiomyocytes pyroptosis plays a crucial part in progression of acute myocardial infarction (MI). GDF11 (Growth Differentiation Factor 11) has been reported to generate cytoprotective effects in phylogenesis and multiple diseases, but the mechanism that GDF11 contributes to cardioprotection of MI and cardiomyocytes pyroptosis remains poorly understood. In our study, we first determined that GDF11 was abnormally downregulated in the heart tissue of MI mice and hypoxic cardiomyocytes. Moreover, AAV9-GDF11 markedly alleviated heart function in MI mice. Meanwhile, GDF11 overexpression also decreased the pyroptosis of hypoxic cardiomyocytes. PROMO and JASPAR prediction software found that transcription factor HOXA3 was predicted as an important regulator of NLRP3, and was confirmed by ChIP assay. Further analysis identifying GDF11 promoted the Smad2/3 pathway resulted in HOXA3 overexpression. Taken together, our study implies that GDF11 prevents cardiomyocytes pyroptosis via HOXA3/NLRP3 signaling pathway in MI mice.

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“…23,24 Li et al found that the pathological silencing of miR-32 could improve hepatic fibrosis. 25 However, there was no direct evidence to support the role of miR-32 in DN fibrosis. In this study, we observe that miR-32 overexpression potentiates EMT process in HG-incubated HK-2 cells, exhibited by the upregulation of α-SMA and vimentin expressions as well as the downregulation of E-cadherin expression.…”

Section: Discussionmentioning

confidence: 99%

“…Increased expression of miR-32 was found in type Ⅱ diabetes patients with obesity and streptozotocin (STZ)-induced diabetic rats. 9,10 A previous study revealed that miR-32 level was obviously enhanced in kidney tissue during chronic allograft dysfunction with interstitial fibrosis and tubular atrophy, 11 implying that miR-32 may be associated with renal fibrosis. However, the role and underlying mechanisms of miR-32 are elusive in DN.…”

Section: Introductionmentioning

confidence: 99%

MiR-32-5p knockdown inhibits epithelial to mesenchymal transition and renal fibrosis by targeting SMAD7 in diabetic nephropathy

et al. 2020

Hum Exp Toxicol

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Diabetic nephropathy (DN) is primary cause of end-stage renal disease. A previous study has shown that miR-32-5p (miR-32) is highly expressed in kidney tissue during chronic allograft dysfunction with interstitial fibrosis and tubular atrophy. However, the role of miR-32-5p (miR-32) in DN is still unclear. In this study, streptozotocin-induced DN rat models and high glucose (HG)-incubated human kidney proximal tubular epithelial (HK-2) cells were established to investigate the role and underlying mechanisms of miR-32 in DN. Results of real-time PCR revealed that miR-32 levels were greatly increased in DN rats and HG-incubated HK-2 cells. Downregulation of miR-32 effectively relieved HG-induced autophagy suppression, fibrosis, epithelial-mesenchymal transition (EMT) and inflammation in HK-2 cells. Besides, miR-32 overexpression significantly down-regulated the expression of mothers against decapentaplegic homolog 7 (SMAD7), whereas knockdown of miR-32 markedly up-regulated the level of SMAD7. Dual-luciferase reporter gene assay confirmed that SMAD7 was a target of miR-32. Reintroduction of SMAD7 expression rescued miR-32-induced HK-2 cells autophagy suppression, EMT and renal fibrosis. Our findings indicate that miR-32 may play roles in the progression of EMT and fibrosis in DN.

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High glucose promotes hepatic fibrosis via miR‑32/MTA3‑mediated epithelial‑to‑mesenchymal transition

Cited by 8 publications

References 44 publications

TGF‐β1 mediated Smad signaling pathway and EMT in hepatic fibrosis induced by Nano NiO in vivo and in vitro

TGF‐β1 mediated Smad signaling pathway and EMT in hepatic fibrosis induced by Nano NiO in vivo and in vitro

GDF11 inhibits cardiomyocyte pyroptosis and exerts cardioprotection in acute myocardial infarction mice by upregulation of transcription factor HOXA3

MiR-32-5p knockdown inhibits epithelial to mesenchymal transition and renal fibrosis by targeting SMAD7 in diabetic nephropathy

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