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Nox2 contributes to cardiac fibrosis in diabetic cardiomyopathy in a transforming growth factor-β dependent manner
1Department of Health Care, The Forth People's Hospital of Jinan City Jinan 250031, China.
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.
Insights
This study shows that Nox2 promotes cardiac fibrosis by increasing collagen production through specific signaling pathways, particularly in response to TGF-β stimulation in diabetic heart disease models.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Cellular Signaling
Background:
- Cardiac fibrosis is a key pathological feature in diabetic cardiomyopathy (DCM).
- The role of NADPH oxidase 2 (Nox2) in cardiac fibrosis development remains incompletely understood.
- Investigating Nox2's regulatory mechanisms is crucial for understanding DCM pathogenesis.
Purpose of the Study:
- To investigate the effect of Nox2 on cardiac fibrosis.
- To elucidate the regulatory mechanism of Nox2 in DCM development.
- To determine Nox2's role in collagen synthesis and associated signaling pathways.
Main Methods:
- Established normal and insulin-resistant cardiac fibroblast models.
- Utilized Nox2-specific siRNA to suppress Nox2 expression.
- Stimulated cells with transforming growth factor-β (TGF-β) and analyzed gene and protein expression via qRT-PCR and Western blot.
Main Results:
- TGF-β stimulation significantly upregulated Nox2 expression at both mRNA and protein levels.
- Nox2 suppression markedly reduced collagen type I and III (COL I and III) expression in TGF-β stimulated cells.
- Nox2 suppression decreased PI3K/AKT and PKC/Rho signaling pathway proteins in insulin-resistant, TGF-β stimulated cells.
Conclusions:
- Nox2 promotes collagen synthesis (COL I and III) in a TGF-β dependent manner.
- The PI3K/AKT and PKC/Rho signaling pathways are involved in Nox2-mediated cardiac fibrosis.
- Nox2 plays a significant role in the pathogenesis of cardiac fibrosis in DCM.
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