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Chitinase 1 regulates pulmonary fibrosis by modulating TGF-β/SMAD7 pathway via TGFBRAP1 and FOXO3

Authors
 Chang-Min Lee  ;  Chuan-Hua He  ;  Jin Wook Park  ;  Jae Hyun Lee  ;  Suchita Kamle  ;  Bing Ma  ;  Bedia Akosman  ;  Roberto Cotez  ;  Emily Chen  ;  Yang Zhou  ;  Erica L Herzog  ;  Changwan Ryu  ;  Xueyan Peng  ;  Ivan O Rosas  ;  Sergio Poli  ;  Carol Feghali Bostwick  ;  Augustine M Choi  ;  Jack A Elias  ;  Chun Geun Lee 
Citation
 Life Science Alliance, Vol.2(3) : e201900350, 2019 
Journal Title
LIFE SCIENCE ALLIANCE
Issue Date
2019
Abstract
TGF-β1 is a critical mediator of tissue fibrosis in health and disease whose effects are augmented by chitinase 1 (CHIT1). However, the mechanisms that CHIT1 uses to regulate TGF-β1-mediated fibrotic responses have not been defined. Here, we demonstrate that CHIT1 enhances TGF-β1-stimulated fibrotic cellular and tissue responses and TGF-β1 signaling. Importantly, we also demonstrate that these effects are mediated by the ability of CHIT1 to inhibit TGF-β1 induction of its feedback inhibitor, SMAD7. CHIT1 also interacted with TGF-β receptor associated protein 1 (TGFBRAP1) and forkhead box O3 (FOXO3) with TGFBRAP1 playing a critical role in CHIT1 enhancement of TGF-β1 signaling and effector responses and FOXO3 playing a critical role in TGF-β1 induction of SMAD7. These pathways were disease relevant because the levels of CHIT1 were increased and inversely correlated with SMAD7 in tissues from patients with idiopathic pulmonary fibrosis or scleroderma-associated interstitial lung disease. These studies demonstrate that CHIT1 regulates TGF-β1/SMAD7 axis via TGFBRAP1 and FOXO3 and highlight the importance of these pathways in the pathogenesis of pulmonary fibrosis.
Files in This Item:
T201904259.pdf Download
DOI
10.26508/lsa.201900350
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Jae Hyun(이재현) ORCID logo https://orcid.org/0000-0002-0760-0071
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/173183
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