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Hepatocyte nuclear factor 4α negatively regulates connective tissue growth factor during liver regeneration.
| Content Provider | Europe PMC |
|---|---|
| Author | Zhou, Junmei Sun, Xiaowei Yang, Lu Wang, Liqun Ran, Gai Wang, Jinhui Cao, Qi Wu, Lizi Bryant, Andrew Ling, Chen Pi, Liya |
| Abstract | AbstractLiver regeneration after injury requires fine‐tune regulation of connective tissue growth factor (Ctgf). It also involves dynamic expression of hepatocyte nuclear factor (Hnf)4α, Yes‐associated protein (Yap), and transforming growth factor (Tgf)‐β. The upstream inducers of Ctgf, such as Yap, etc, are well‐known. However, the negative regulator of Ctgf remains unclear. Here, we investigated the Hnf4α regulation of Ctgf post‐various types of liver injury. Both wild‐type animals and animals contained siRNA‐mediated Hnf4α knockdown and Cre‐mediated Ctgf conditional deletion were used. We observed that Ctgf induction was associated with Hnf4α decline, nuclear Yap accumulation, and Tgf‐β upregulation during early stage of liver regeneration. The Ctgf promoter contained an Hnf4α binding sequence that overlapped with the cis‐regulatory element for Yap and Tgf‐β. Ctgf loss attenuated inflammation, hepatocyte proliferation, and collagen synthesis, whereas Hnf4α knockdown enhanced Ctgf induction and liver fibrogenesis. These findings provided a new mechanism about fine‐tuned regulation of Ctgf through Hnf4α antagonism of Yap and Tgf‐β activities to balance regenerative and fibrotic signals. |
| Related Links | https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC7722640&blobtype=pdf |
| Page Count | 14 |
| ISSN | 08926638 |
| Journal | The FASEB Journal [FASEB J] |
| Volume Number | 34 |
| PubMed Central reference number | PMC7722640 |
| Issue Number | 4 |
| PubMed reference number | 32057145 |
| e-ISSN | 15306860 |
| DOI | 10.1096/fj.201902382r |
| Language | English |
| Publisher | John Wiley and Sons Inc. |
| Publisher Date | 2020-02-14 |
| Publisher Place | Hoboken |
| Access Restriction | Open |
| Rights License | This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. © 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology. |
| Subject Keyword | connective tissue growth factor (Ctgf) hepatocyte nuclear factor 4α (Hnf4α) liver injury liver regeneration |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Medicine Molecular Biology Biochemistry Biotechnology |
