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The ASIC3-M-CSF-M2 macrophage-positive feedback loop modulates fibroblast-to-myofibroblast differentiation in skin fibrosis pathogenesis.


ABSTRACT: Inflammation is one of the main pathological features leading to skin fibrosis and a key factor leading to the progression of skin fibrosis. Acidosis caused by a decrease in extracellular pH is a sign of the inflammatory process. Acid-sensing ion channels (ASICs) are ligand-gated ion channels on the cell membrane that sense the drop in extracellular pH. The molecular mechanisms by which skin fibroblasts are regulated by acid-sensing ion channel 3 (ASIC3) remain unknown. This study investigated whether ASIC3 is related to inflammation and skin fibrosis and explored the underlying mechanisms. We demonstrate that macrophage colony-stimulating factor (M-CSF) is a direct target of ASIC3, and ASIC3 activation promotes M-CSF transcriptional regulation of macrophages for M2 polarization. The polarization of M2 macrophages transduced by the ASIC3-M-CSF signal promotes the differentiation of fibroblasts into myofibroblasts through transforming growth factor β1 (TGF-β1), thereby producing an ASIC3-M-CSF-TGF-β1 positive feedback loop. Targeting ASIC3 may be a new treatment strategy for skin fibrosis.

SUBMITTER: Wu JJ 

PROVIDER: S-EPMC9167818 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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The ASIC3-M-CSF-M2 macrophage-positive feedback loop modulates fibroblast-to-myofibroblast differentiation in skin fibrosis pathogenesis.

Wu Jun-Jie JJ   Sun Zi-Li ZL   Liu Si-Yu SY   Chen Zhong-Hua ZH   Yuan Zheng-Dong ZD   Zou Ming-Li ML   Teng Ying-Ying YY   Li Yue-Yue YY   Guo Dan-Yang DY   Yuan Feng-Lai FL  

Cell death & disease 20220606 6


Inflammation is one of the main pathological features leading to skin fibrosis and a key factor leading to the progression of skin fibrosis. Acidosis caused by a decrease in extracellular pH is a sign of the inflammatory process. Acid-sensing ion channels (ASICs) are ligand-gated ion channels on the cell membrane that sense the drop in extracellular pH. The molecular mechanisms by which skin fibroblasts are regulated by acid-sensing ion channel 3 (ASIC3) remain unknown. This study investigated w  ...[more]

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