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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2020.1
- 수록면
- 671 - 682 (12page)
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Background: This study investigated whether xenotransplantation of human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) reduces thioacetamide (TAA)-induced mouse liver fibrosis and the underlying molecular mechanism. Methods: Recipient NOD/SCID mice were injected intraperitoneally with TAA twice weekly for 6 weeks before initial administration of WJ-MSCs. Expression of regenerative and pro-fibrogenic markers in mouse fibrotic livers were monitored post cytotherapy. A hepatic stallate cell line HSC-T6 and isolated WJ-MSCs were used for in vitro adhesion, migration and mechanistic studies. Results: WJ-MSCs were isolated from human umbilical cords by an explant method and characterized by flow cytometry. A single infusion of WJ-MSCs to TAA-treated mice significantly reduced collagen deposition and ameliorated liver fibrosis after 2-week therapy. In addition to enhanced expression of hepatic regenerative factor, hepatocyte growth factor, and PCNA proliferative marker, WJ-MSC therapy significantly blunted pro-fibrogenic signals, including Smad2, RhoA, ERK. Intriguingly, reduction of plasma fibronectin (pFN) in fibrotic livers was noted in MSC-treated mice. In vitro studies further demonstrated that suspending MSCs triggered pFN degradation, soluble pFN conversely retarded adhesion of suspending MSCs onto type I collagen-coated surface, whereas pFN coating enhanced WJ-MSC migration across mimicked wound bed. Moreover, pretreatment with soluble pFN and conditioned medium from MSCs with pFN strikingly attenuated the response of HSC-T6 cells to TGF-β1-stimulation in Smad2 phosphorylation and RhoA upregulation. Conclusion: These findings suggest that cytotherapy using WJ-MSCs may modulate hepatic pFN deposition for a better regenerative niche in the fibrotic livers and may constitute a useful anti-fibrogenic intervention in chronic liver diseases.
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참고문헌 (54)
참고문헌 신청
Bissell DM / 1998 / Hepatic fibrosis as wound repair : a progress report / J Gastroenterol 33:295~302
Tsukada S / 2006 / Mechanisms of liver fibrosis / Clin Chim Acta 364:33~60
Friedman SL / 1997 / Molecular mechanisms of hepatic fibrosis and principles of therapy / J Gastroenterol 32:424~430
Qian J / 2012 / b-Catenin pathway is required for TGF-b inhibition of PPARgamma expression in cultured hepatic stellate cells / Pharmacol Res 66:219~225
Deng X / 2016 / Post-translational modification of CREB-1 decreases collagen I expression by inhibiting the TGF-b1 signaling pathway in rat hepatic stellate cells / Mol Med Rep 14:5751~5759
Tsukada S / 2006 / Mechanisms of liver fibrosis / Clin Chim Acta 364:33~60
Friedman SL / 1997 / Molecular mechanisms of hepatic fibrosis and principles of therapy / J Gastroenterol 32:424~430
Qian J / 2012 / b-Catenin pathway is required for TGF-b inhibition of PPARgamma expression in cultured hepatic stellate cells / Pharmacol Res 66:219~225
Deng X / 2016 / Post-translational modification of CREB-1 decreases collagen I expression by inhibiting the TGF-b1 signaling pathway in rat hepatic stellate cells / Mol Med Rep 14:5751~5759
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