Yanagihara, Toyoshi, Tsubouchi, Kazuya, Zhou, Quan, Chong, Michael, Otsubo, Kohei, Isshiki, Takuma, Schupp, Jonas C, Sato, Seidai, Scallan, Ciaran, Upagupta, Chandak, Revill, Spencer, Ayoub, Anmar, Chong, Sy Giin, Dvorkin-Gheva, Anna, Kaminski, Naftali, Tikkanen, Jussi, Keshavjee, Shaf, Paré, Guillaume, Guignabert, Christophe, Ask, Kjetil and Kolb, Martin R J (2023) Vascular-Parenchymal Cross-Talk Promotes Lung Fibrosis through BMPR2 Signaling. American journal of respiratory and critical care medicine, 207 (11). pp. 1498-1514. ISSN 1535-4970

Abstract

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by progressive lung scarring. IPF-related pulmonary vascular remodeling and pulmonary hypertension (PH) result in a particularly poor prognosis. To study the pathogenesis of vascular remodeling in fibrotic lungs and its contribution to progression of fibrosis. We used an experimental model of lung fibrosis associated with PH by transient overexpression of active TGF-β1 (transforming growth factor-β1). Samples from patients with fibrotic lung diseases were analyzed in depth using immunostaining, gene expression, and gene mutations. We found a reduction in endothelial cells (ECs) and activation of vascular smooth muscle cells (VSMCs) in fibrotic lungs. Coculturing fibroblasts with VSMCs or ECs from fibrotic lungs induced fibrotic phenotypes in fibroblasts. IPF fibroblasts induced EC death and activation of VSMCs in coculture systems. Decreased concentrations of BMPR2 (bone morphogenic protein receptor 2) and its signaling were observed

Item Type:	Article
Date Deposited:	28 Dec 2024 00:45
Last Modified:	28 Dec 2024 00:45
URI:	https://oak.novartis.com/id/eprint/56185