| First Author | Zhou J | Year | 2020 |
| Journal | FASEB J | Volume | 34 |
| Issue | 4 | Pages | 4970-4983 |
| PubMed ID | 32057145 | Mgi Jnum | J:304937 |
| Mgi Id | MGI:6695379 | Doi | 10.1096/fj.201902382R |
| Citation | Zhou J, et al. (2020) Hepatocyte nuclear factor 4alpha negatively regulates connective tissue growth factor during liver regeneration. FASEB J 34(4):4970-4983 |
| abstractText | Liver regeneration after injury requires fine-tune regulation of connective tissue growth factor (Ctgf). It also involves dynamic expression of hepatocyte nuclear factor (Hnf)4alpha, Yes-associated protein (Yap), and transforming growth factor (Tgf)-beta. The upstream inducers of Ctgf, such as Yap, etc, are well-known. However, the negative regulator of Ctgf remains unclear. Here, we investigated the Hnf4alpha regulation of Ctgf post-various types of liver injury. Both wild-type animals and animals contained siRNA-mediated Hnf4alpha knockdown and Cre-mediated Ctgf conditional deletion were used. We observed that Ctgf induction was associated with Hnf4alpha decline, nuclear Yap accumulation, and Tgf-beta upregulation during early stage of liver regeneration. The Ctgf promoter contained an Hnf4alpha binding sequence that overlapped with the cis-regulatory element for Yap and Tgf-beta. Ctgf loss attenuated inflammation, hepatocyte proliferation, and collagen synthesis, whereas Hnf4alpha knockdown enhanced Ctgf induction and liver fibrogenesis. These findings provided a new mechanism about fine-tuned regulation of Ctgf through Hnf4alpha antagonism of Yap and Tgf-beta activities to balance regenerative and fibrotic signals. |
