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Alveolar epithelial cell‐derived Sonic hedgehog promotes pulmonary fibrosis through OPN‐dependent alternative macrophage activation
Author(s) -
Hou Jiwei,
Ji Jie,
Chen Xiang,
Cao Honghui,
Tan Yi,
Cui Yu,
Xiang Zou,
Han Xiaodong
Publication year - 2021
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15669
Subject(s) - paracrine signalling , pulmonary fibrosis , sonic hedgehog , macrophage , fibrosis , cancer research , macrophage polarization , autocrine signalling , microbiology and biotechnology , biology , immunology , pathology , signal transduction , medicine , receptor , biochemistry , in vitro
Alveolar epithelial cell‐derived Sonic hedgehog (Shh) promotes pulmonary fibrosis through osteopontin (OPN)‐dependent alternative macrophage activation. Fibrosis‐associated ATII cells secrete Shh, a hedgehog pathway ligand, and that ATII cell‐derived Shh promotes the secretion of OPN in macrophages via Shh/Gli signaling cascade. The secreted OPN acts on the surrounding macrophages in an autocrine or paracrine manner and induces macrophage alternative activation through activating the JAK2/STAT3 signaling pathway, eventually leading to pulmonary fibrogenesis.