| First Author | Fan W | Year | 2022 |
| Journal | Cell Rep | Volume | 41 |
| Issue | 2 | Pages | 111454 |
| PubMed ID | 36223738 | Mgi Jnum | J:330378 |
| Mgi Id | MGI:7366842 | Doi | 10.1016/j.celrep.2022.111454 |
| Citation | Fan W, et al. (2022) Estrogen receptor beta activation inhibits colitis by promoting NLRP6-mediated autophagy. Cell Rep 41(2):111454 |
| abstractText | Estrogen receptor beta (ERbeta) and NOD-like receptor family pyrin domain containing 6 (NLRP6) are highly expressed in intestinal tissues. Loss of ERbeta and NLRP6 exacerbate colitis in mouse models; however, the underlying mechanisms are incompletely understood. Here, we report that ERbeta directly activates the NLRP6 gene expression via binding to estrogen responsive element of Nlrp6 gene promoter. ERbeta also physically interacts with the NLRP6 nucleotide-binding domain and promotes NLRP6 inflammasome assembly. The ERbeta-NLRP6 axis then interacts with multiple autophagy-related proteins, including ULK1, BECN1, ATG16L1, LC3B, and p62, and affects the autophagosome biogenesis and autophagic flux. Finally, NLRP6-mediated autophagy suppresses the inflammatory response by promoting the K48-linked polyubiquitination of ASC, Casp-1 p20, IL-1beta, TNF-alpha, and prohibitin-2. Thus, ERbeta-NLRP6 direct an anti-inflammatory response by promoting autophagy. Our work uncovers an ERbeta-NLRP6-autophagy pathway as a regulatory mechanism that maintains intestinal epithelial cell homeostasis and facilitates tissue repair in colitis. |
