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Niche-Dependent Regulation of Lkb1 in the Proliferation of Lung Epithelial Progenitor Cells
oleh: Qingwen Ma, Xue Li, Sisi Wang, Qi Wang, Yu Li, Kuan Li, Jianhai Wang, Qiuyang Zhang, Junping Wu, Huaiyong Chen
| Format: | Article |
|---|---|
| Diterbitkan: | MDPI AG 2022-12-01 |
Deskripsi
Lung homeostasis and regeneration depend on lung epithelial progenitor cells. <i>Lkb1</i> (Liver Kinase B1) has known roles in the differentiation of airway epithelial cells during embryonic development. However, the effects of <i>Lkb1</i> 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 <i>Lkb1</i> regulates lung epithelial progenitor cell regeneration. Organoid culture showed that loss of <i>Lkb1</i> significantly reduced the proliferation of club cells and alveolar type 2 (AT2) cells in vitro. In the absence of <i>Lkb1</i>, 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 <i>Claudin-18</i> was obviously reduced in AT2 cells after <i>Lkb1</i> knockdown. On the whole, our findings indicated that <i>Lkb1</i> 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.