PT - JOURNAL ARTICLE AU - Lee, Chang-Min AU - He, Chuan-Hua AU - Park, Jin Wook AU - Lee, Jae Hyun AU - Kamle, Suchitra AU - Ma, Bing AU - Akosman, Bedia AU - Cotez, Roberto AU - Chen, Emily AU - Zhou, Yang AU - Herzog, Erica L AU - Ryu, Changwan AU - Peng, Xueyan AU - Rosas, Ivan O AU - Poli, Sergio AU - Bostwick, Carol Feghali AU - Choi, Augustine M AU - Elias, Jack A AU - Lee, Chun Geun TI - Retraction: Chitinase 1 regulates pulmonary fibrosis by modulating TGF-β/SMAD7 pathway via TGFBRAP1 and FOXO3 AID - 10.26508/lsa.201900350 DP - 2019 Jun 01 TA - Life Science Alliance PG - e201900350 VI - 2 IP - 3 4099 - https://www.life-science-alliance.org/content/2/3/e201900350.short 4100 - https://www.life-science-alliance.org/content/2/3/e201900350.full SO - Life Sci. Alliance2019 Jun 01; 2 AB - 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.