Dataset Information

NOX4-Derived ROS Promotes Collagen I Deposition in Bronchial Smooth Muscle Cells by Activating Noncanonical p38MAPK/Akt-Mediated TGF-β Signaling.

ABSTRACT:

Background

Airway smooth muscle (ASM) remodeling is a hallmark in chronic obstructive pulmonary disease (COPD). NADPH oxidase 4- (NOX4-) mediated reactive oxygen species (ROS) production plays a crucial role in cell differentiation and extracellular matrix (ECM) synthesis in ASM remodeling. However, the precise mechanisms underpinning its pathogenic roles remain elusive.

Methods

The expression of NOX4 and TGF-β ₁ in the airway of the lung was measured in COPD patients and the control group. Cigarette smoke- (CS-) induced emphysema mice were generated, and the alteration of α-SMA, NOX4, TGF-β ₁, and collagen I was accessed. The changes of the expression of ECM markers, NOX4, components of TGF-β/Smad, and MAPK/Akt signaling in human bronchial smooth muscle cells (HBSMCs) were ascertained for delineating mechanisms of NOX4-mediated ROS production on cell differentiation and remodeling in human ASM cells.

Results

An increased abundance of NOX4 and TGF-β ₁ proteins in the epithelial cells and ASM of lung was observed in COPD patients compared with the control group. Additionally, an increased abundance expression of NOX4 and α-SMA was observed in the lungs of the CS-induced emphysema mouse model. TGF-β ₁ displayed abilities to increase the oxidative burden and collagen I production, along with enhanced phosphorylation of ERK, p38MAPK, and p-Akt473 in HBSMCs. These effects of TGF-β ₁ could be inhibited by the ROS scavenger N-acetylcysteine (NAC), siRNA-mediated knockdown of Smad3 and NOX4, and pharmacological inhibitors SB203580 (p38MAPK inhibitor) and LY294002 (Akt inhibitor).

Conclusions

NOX4-mediated ROS production alters TGF-β ₁-induced cell differentiation and collagen I protein synthesis in HBSMCs in part through the p38MAPK/Akt signaling pathway in a Smad-dependent manner.

SUBMITTER: Hao B

PROVIDER: S-EPMC8007363 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

NOX4-Derived ROS Promotes Collagen I Deposition in Bronchial Smooth Muscle Cells by Activating Noncanonical p38MAPK/Akt-Mediated TGF-<i>β</i> Signaling.

Hao Binwei B Sun Ruiting R Guo Xiaotong X Zhang Lili L Cui Jieda J Zhou Yumin Y Hong Wei W Zhang Yanan Y He Jinxi J Liu Xiaoming X Li Bing B Ran Pixin P Chen Juan J

Oxidative medicine and cellular longevity 20210319

<h4>Background</h4>Airway smooth muscle (ASM) remodeling is a hallmark in chronic obstructive pulmonary disease (COPD). NADPH oxidase 4- (NOX4-) mediated reactive oxygen species (ROS) production plays a crucial role in cell differentiation and extracellular matrix (ECM) synthesis in ASM remodeling. However, the precise mechanisms underpinning its pathogenic roles remain elusive.<h4>Methods</h4>The expression of NOX4 and TGF-<i>β</i> <sub>1</sub> in the airway of the lung was measured in COPD pat ...[more]

PMID: 33824697

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