Connective tissue growth factor induces hepatic progenitor cells to differentiate into hepatocytes

Yang,Ai-Ting; Wang,Ping; Tong,Xiao-Fei; Cong,Min; Liu,Tian-Hui; Cong,Rui; Wu,Peng; Jia,Ji-Dong; Wang,Bao-En; You,Hong

doi:10.3892/ijmm.2013.1380

July 2013 Volume 32 Issue 1

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July 2013 Volume 32 Issue 1

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Article

Connective tissue growth factor induces hepatic progenitor cells to differentiate into hepatocytes

Authors:
- Ai-Ting Yang
- Ping Wang
- Xiao-Fei Tong
- Min Cong
- Tian-Hui Liu
- Rui Cong
- Peng Wu
- Ji-Dong Jia
- Bao-En Wang
- Hong You
View Affiliations / Copyright

Affiliations: Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, P.R. China
Pages: 35-42
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Published online on: May 13, 2013

https://doi.org/10.3892/ijmm.2013.1380
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Abstract

Connective tissue growth factor (CTGF) plays an important role in the proliferation of hepatic progenitors, however, little is known concerning the mechanism(s) through which it influences their differentiation. The differentiation of hepatic progenitors (WB-F344), either stimulated with recombinant CTGF or stably transfected with a CTGF overexpression plasmid, was investigated. Expression of the differentiation markers α-fetoprotein (AFP), albumin (ALB) and cytokeratin-19 (CK-19) was assessed. To confirm the effects of CTGF on progenitor differentiation, cells were treated with an inhibitor (WP631) of CTGF. Treatment of WB-F344 cells with recombinant CTGF for 24 h did not change the survival rate significantly, but the progenitors were enlarged with a decreased nuclear/cytoplasmic ratio. CTGF downregulated the expression of the fetal hepatocyte marker, AFP, while it upregulated the mature hepatocyte cell marker, ALB. The effect of CTGF overexpression plasmid on WB-F344 cell differentiation was consistent with a pattern of direct CTGF stimulation, including decreased AFP and increased ALB expression. Furthermore, the suppression of CTGF induction by an inhibitor was associated with significant inhibition of hepatic progenitor cell differentiation into hepatocytes. Importantly, we showed that differentiated WB-F344 cells by CTGF had in vitro functions characteristic of hepatocytes, including ALB production, glycogen storage and cytochrome P450 activity. Both recombinant CTGF and the CTGF overexpression plasmid induced hepatic progenitor differentiation into hepatocytes. This was suppressed by the CTGF inhibitor.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Connective tissue growth factor induces hepatic progenitor cells to differentiate into hepatocytes

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Abstract

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