| Popis: |
Family with Sequence Similarity 13, Member A (FAM13A), consistently associated with COPD by Genome-wide association studies (GWAS), is mainly expressed in the lung epithelial progenitors including Club cells and alveolar type II epithelial (ATII) cells. Fam13a-/- mice are resistant to cigarette smoke (CS)–induced emphysema. Herein, we ask when and where FAM13A regulates the Wnt pathway, the requisite pathway for alveolar epithelial repair, in vivo during CS exposure in lung epithelial progenitors. Indeed, FAM13A-deficiency significantly increased Wnt activation mainly in lung epithelial cells. Consistently, after long-term CS exposure in vivo, FAM13A deficiency bestows alveolar epithelial progenitor cells with enhanced proliferation and differentiation in the ex vivo organoid model. Importantly, expression of FAM13A is significantly increased in human COPD-derived ATII cells compared to healthy ATII cells as suggested by single cell RNA-sequencing data. These results suggest that FAM13A-deficiency promotes the Wnt pathway-mediated ATII cell repair/regeneration, and thereby possibly mitigating CS-induced alveolar destruction. Funding Statement: This work was supported by U.S. National Institutes of Health (NIH) grants R01HL127200, R01HL137927, R01HL148667 and R01HL147148 to X.Z. Declaration of Interests: The authors have declared that no conflict of interest exists. Ethics Approval Statement: Mouse experiments were performed under IACUC guidelines and approved protocols at Brigham and Women’s Hospital. |
