The noncanonical BMP signaling pathway plays an important role in club cell regeneration

Schematic representation of our results showing the critical roles of the noncanonical signaling pathway of BMPs, (BMPR1A ‐Tak1‐p38MAPK) in club cell regeneration. Naphthalene (NA) is metabolized by CYP‐2F2, which is expressed exclusively in club cells, generating cytotoxic epoxide that kills the club cells within 1.5 days after NA exposure. Under normal conditions, hyperplastic growth occurs at day 3 and the b ronchiolar epithelium is restored at day 7. We show that ablation ofBmpr1a,Tak1, orMapk14 (encoding p38 α) in club cells resulted in severe defects in regeneration and bronchiole repair in adult mice. AbstractThe bronchiole is a major site for the development of several life ‐threatening disorders including chronic obstructive pulmonary disease and lung adenocarcinomas. The bronchiolar epithelium is composed of club cells and ciliated epithelial cells, with club cells serving as progenitor cells. Presently, the identity of the cells involved in regeneration of bronchi olar epithelium and the underlying mechanisms remain incompletely understood. Here, we show that Prrx1, a homeobox transcription factor, can mark club cells in adult mice during homeostasis and regeneration. We further show that the noncanonical signaling pathway of BMPs, BMPR1A‐Tak1‐p38MAPK, pl ays a critical role in club cell regeneration. Ablation ofBmpr1a,Tak1, orMapk14 (encoding p38 α) in Prrx1+ club cells caused minimal effect on bronchiolar epithelium homeostasis, yet it resulted in...
Source: Stem Cells - Category: Stem Cells Authors: Tags: TISSUE ‐SPECIFIC STEM CELLS Source Type: research