The Role of SOX9 in IGF-II-Mediated Pulmonary Fibrosis

Pulmonary fibrosis (PF) associated with systemic sclerosis (SSc) results in significant morbidity and mortality. We previously reported that insulin-like growth factor-II (IGF-II) is overexpressed lung tissues fibroblasts from SSc patients, IGF-II fosters by upregulating collagen type I, fibronectin, TGFβ. now show augments mRNA levels of profibrotic signaling molecules TGFβ2 (p ≤ 0.01) TGFβ3 0.05), III 0.01), the posttranslational modification enzymes P4HA2 P3H2 LOX = 0.065), LOXL2 LOXL4 0.05) primary human fibroblasts. increases protein as well COL3A1, P4HA2, P4Hβ, 0.05). In contrast, decreases degradation cathepsin (CTS) K, CTSB, CTSL CTSK The SRY-box transcription factor 9 (SOX9) at compared to healthy controls. induces SOX9 via IGF1R/IR hybrid receptor, regulates COL3A1 0.001) downstream IGF-II. Our identify a novel axis targets are regulated SOX9-dependent -independent manner. findings provide insights on role promoting pulmonary fibrosis.