Other
17 Authors
- Wang Y,
- Crawford SE,
- Luo J,
- Cui K,
- Wu C,
- Chen Z,
- Wang S,
- Ren X,
- Zhu J,
- Castro-Martinez F,
- Li J,
- Kim G,
- Wisniewski J,
- Becerra SP,
- Liu T,
- Zhao K,
- Sun J
| First Author | Kim G | Year | 2024 |
| Journal | Cell | Volume | 187 |
| Issue | 4 | Pages | 914-930.e20 |
| PubMed ID | 38280375 | Mgi Jnum | J:348747 |
| Mgi Id | MGI:7613860 | Doi | 10.1016/j.cell.2024.01.001 |
| Citation | Kim G, et al. (2024) Gut-liver axis calibrates intestinal stem cell fitness. Cell 187(4):914-930.e20 |
| abstractText | The gut and liver are recognized to mutually communicate through the biliary tract, portal vein, and systemic circulation. However, it remains unclear how this gut-liver axis regulates intestinal physiology. Through hepatectomy and transcriptomic and proteomic profiling, we identified pigment epithelium-derived factor (PEDF), a liver-derived soluble Wnt inhibitor, which restrains intestinal stem cell (ISC) hyperproliferation to maintain gut homeostasis by suppressing the Wnt/beta-catenin signaling pathway. Furthermore, we found that microbial danger signals resulting from intestinal inflammation can be sensed by the liver, leading to the repression of PEDF production through peroxisome proliferator-activated receptor-alpha (PPARalpha). This repression liberates ISC proliferation to accelerate tissue repair in the gut. Additionally, treating mice with fenofibrate, a clinical PPARalpha agonist used for hypolipidemia, enhances colitis susceptibility due to PEDF activity. Therefore, we have identified a distinct role for PEDF in calibrating ISC expansion for intestinal homeostasis through reciprocal interactions between the gut and liver. |
