LTBP2: A Potential Fibroblasts-Anchoring Target in Idiopathic Pulmonary Fibrosis Regulated by TCF4

<bold>Purpose:</bold> Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease with unknown cause, characterized by excessive accumulation of fibroblasts and deposition of extracellular matrix, disrupting lung function. Recent evidence suggests high latent transforming growth factor β binding protein 2 (LTBP2) expression in IPF, potentially regulating lung fibroblasts functions. This study aimed to investigate the effects and molecular mechanism of LTBP2 in IPF. <bold>Methods:</bold> GSE122960 single-cell RNA sequencing data of IPF was obtained from GEO database. IPF and healthy donor lung tissue samples were acquired from the First Affiliated Hospital of Zhengzhou University. Moreover, in vitro experiments were conducted to verify the regulatory role and mechanism of LTBP2 in IPF. <bold>Results:</bold> LTBP2 was up-regulated in fibroblasts of IPF. Low expression of LTBP2 can inhibit differentiation of lung fibroblasts to myofibroblasts in vitro. Knocking down LTBP2 can inhibit the proliferation and migration ability of TGF-β1 dependent lung fibroblasts. LTBP2 is regulated by transcription factor 4 (TCF4). <bold>Conclusions:</bold> LTBP2 silencing can inhibit differentiation of lung fibroblasts to myofibroblasts and weaken proliferation and migration ability of fibroblasts/myofibroblasts, which is regulated by TCF4.