Hepatocyte-specific Prominin-1 protects against liver injury-induced fibrosis by stabilizing SMAD7

Hyun Lee, Dong Min Yu, Myeong Suk Bahn, Young Jae Kwon, Min Jee Um, Seo Yeon Yoon, Ki Tae Kim, Myoung Woo Lee, Sung Je Jo, Sungsoo Lee, Seung Hoi Koo, Ki Hoon Jung, Jae Seon Lee, Young Gyu Ko

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Prominin-1 (PROM1), also known as CD133, is expressed in hepatic progenitor cells (HPCs) and cholangiocytes of the fibrotic liver. In this study, we show that PROM1 is upregulated in the plasma membrane of fibrotic hepatocytes. Hepatocellular expression of PROM1 was also demonstrated in mice (Prom1CreER; R26TdTom) in which cells expressed TdTom under control of the Prom1 promoter. To understand the role of hepatocellular PROM1 in liver fibrosis, global and liver-specific Prom1-deficient mice were analyzed after bile duct ligation (BDL). BDL-induced liver fibrosis was aggravated with increased phosphorylation of SMAD2/3 and decreased levels of SMAD7 by global or liver-specific Prom1 deficiency but not by cholangiocyte-specific Prom1 deficiency. Indeed, PROM1 prevented SMURF2-induced SMAD7 ubiquitination and degradation by interfering with the molecular association of SMAD7 with SMURF2. We also demonstrated that hepatocyte-specific overexpression of SMAD7 ameliorated BDL-induced liver fibrosis in liver-specific Prom1-deficient mice. Thus, we conclude that PROM1 is necessary for the negative regulation of TGFβ signaling during liver fibrosis.

Original languageEnglish
Pages (from-to)1277-1289
Number of pages13
JournalExperimental and Molecular Medicine
Issue number8
Publication statusPublished - 2022 Aug

Bibliographical note

Publisher Copyright:
© 2022, The Author(s).

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry


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