Hepatocyte nuclear factor 4α negatively regulates connective tissue growth factor during liver regeneration
Date
2020Journal
FASEB JournalPublisher
John Wiley and Sons Inc.Type
Article
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Liver 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.Keyword
connective tissue growth factor (Ctgf)hepatocyte nuclear factor 4α (Hnf4α)
liver injury
liver regeneration
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https://www.scopus.com/inward/record.uri?eid=2-s2.0-85079456766&doi=10.1096%2ffj.201902382R&partnerID=40&md5=54dce477471eeaf1a70cc7dbfcf1c3c4; http://hdl.handle.net/10713/12132ae974a485f413a2113503eed53cd6c53
10.1096/fj.201902382R
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