Yanagihara, Toyoshi, Zhou, Quan, Tsubouchi, Kazuya, Revill, Spencer, Ayoub, Anmar, Gholiof, Mahsa, Chong, Sy Giin, Dvorkin-Gheva, Anna, Ask, Kjetil, Shi, Wei and Kolb, Martin Rj (2023) Intrinsic BMP inhibitor Gremlin regulates alveolar epithelial type II cell proliferation and differentiation. Biochemical and biophysical research communications, 656. pp. 53-62. ISSN 1090-2104

Abstract

Type 1 alveolar epithelial cells (AT1s) and type 2 alveolar epithelial cells (AT2s) regulate the structural integrity and function of alveoli. AT1s mediate gas exchange, whereas AT2s serve multiple functions, including surfactant secretion and alveolar repair through proliferation and differentiation into AT1s as progenitors. However, mechanisms regulating AT2 proliferation and differentiation remain unclear. Here we demonstrate that Gremlin, an intrinsic inhibitor of bone morphogenetic protein (BMP), induces AT2 proliferation and differentiation. Transient overexpression of Gremlin in rat lungs by adenovirus vector delivery suppressed BMP signaling, induced proliferation of AT2s and the production of Bmp2, which in turn led to the recovery of BMP signaling and induced AT2 differentiation into AT1s. Bleomycin-induced lung injury upregulated Gremlin and showed a similar time course of biomarker expression comparable to the adenovirus model. TGF-β and IL-1β induced Gremlin expression in fibroblasts. Taken toget

Item Type:	Article
Date Deposited:	28 Dec 2024 00:45
Last Modified:	28 Dec 2024 00:45
URI:	https://oak.novartis.com/id/eprint/56184