Niche-Dependent Regulation of Lkb1 in the Proliferation of Lung Epithelial Progenitor Cells

Abstract

Lung homeostasis and regeneration depend on lung epithelial progenitor cells. Lkb1 (Liver Kinase B1) has known roles in the differentiation of airway epithelial cells during embryonic development. However, the effects of Lkb1 in adult lung epithelial progenitor cell regeneration and its mechanisms of action have not been determined. In this study, we investigated the mechanism by which Lkb1 regulates lung epithelial progenitor cell regeneration. Organoid culture showed that loss of Lkb1 significantly reduced the proliferation of club cells and alveolar type 2 (AT2) cells in vitro. In the absence of Lkb1, there is a slower recovery rate of the damaged airway epithelium in naphthalene-induced airway epithelial injury and impaired expression of surfactant protein C during bleomycin-induced alveolar epithelial damage. Moreover, the expression of autophagy-related genes was reduced in club cells and increased in AT2 cells, but the expression of Claudin-18 was obviously reduced in AT2 cells after Lkb1 knockdown. On the whole, our findings indicated that Lkb1 may promote the proliferation of lung epithelial progenitor cells via a niche-dependent pathway and is required for the repair of the damaged lung epithelium.

Nitric oxide hinders club cell proliferation through Gdpd2 during allergic airway inflammation

“…The direct Gdpd2‐catalytic products, glycerol and Ins1p1, might generate different metabolites via various pathways that differentially regulate club cell functions at steady state versus in allergic airway inflammation. As a regulator of lipid metabolism, Lkb1 regulates club cell proliferation in a niche‐dependent manner [ 43 , 44 ]. Glycerol inhibits cell proliferation but may promote cell proliferation under some pathological conditions.…”