Nox2 contributes to cardiac fibrosis in diabetic cardiomyopathy in a transforming growth factor-β dependent manner.
Year: 2015
Type: article
Abstract: PURPOSE: This study aimed to investigate the effect of Nox2 on cardiac fibrosis and to elucidate the regulatory mechanism of Nox2 in the development of DCM. METHODS: We established normal and insulin-resistant cellular model using neonatal rat cardiac fibroblasts. Then Nox2-specific siRNA were transfected into cardiac fibroblasts with Lipofectamine ® 2000 and crambled siRNA sequence was considered as control. Meanwhile, a part of cells were randomly selected to be treated with or without transforming growth factor-β (TGF-β). Moreover, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were respectively performed to determine the expression level of related molecules, such as Nox2, collagen type I and III (COL I and III) and PI3K/AKT and PKC/Rho signaling pathway-related proteins. RESULTS: TGF-β stimulation significantly increased the expression level of Nox2 both in mRNA and protein levels. Suppression of the Nox2 markedly decreased the expression of COL I and COL III in normal and insulin-resistant cellular model with TGF-β stimulation. Moreover, suppression of the Nox2 significantly decreased the expression of PI3K/AKT and PKC/Rho signaling pathway-related proteins in insulin-resistant cellular model with TGF-β stimulation. However, suppression of Nox2 had no effects on these proteins without TGF-β stimulation. CONCLUSIONS: Our finding reveals that Nox2 may promote synthesis of COL I and III via involved in PI3K/AKT and PKC/Rho signaling pathway in a TGF-β dependent manner and consequently promote cardiac fibrosis in the development of DCM.
Source: PubMed
Authors: Yuqin Liu, Jinhua Zhang
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2192042979