title: Hedgehog-mediated paracrine interaction between hepatic stellate cells and marrow-derived mesenchymal stem cells.
abstract: During liver injury, bone marrow-derived mesenchymal stem cells (MSCs) can migrate and differentiate into hepatocytes. Hepatic stellate cell (SC) activation is a pivotal event in the development of liver fibrosis. Therefore, we hypothesized that SCs may play an important role in regulating MSC proliferation and differentiation through the paracrine signaling pathway. We demonstrate that MSCs and SCs both express hedgehog (Hh) pathway components, including its ligands, receptors, and target genes. Transwell co-cultures of SCs and MSCs showed that the SCs produced sonic hedgehog (Shh), which enhanced the proliferation and differentiation of MSCs. These findings demonstrate that SCs indirectly modulate the activity of MSCs in vitro via the Hh pathway, and provide a plausible explanation for the mechanisms of transplanted MSCs in the treatment of liver fibrosis.
authors.affiliation: Division of Hepatology, The Third Hospital of Sun Yat-Sen University, Tianhe Road 600, Guangzhou City 510630, Guangdong Province, China. linnancn@gmail.com
authors.forename: Nan
authors.initials: N
authors.lastname: Lin
authors.forename: Zhaofeng
authors.initials: Z
authors.lastname: Tang
authors.forename: Meihai
authors.initials: M
authors.lastname: Deng
authors.forename: Yuesi
authors.initials: Y
authors.lastname: Zhong
authors.forename: Jizong
authors.initials: J
authors.lastname: Lin
authors.forename: Xuhui
authors.initials: X
authors.lastname: Yang
authors.forename: Peng
authors.initials: P
authors.lastname: Xiang
authors.forename: Ruiyun
authors.initials: R
authors.lastname: Xu
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D019899:Paracrine Communication; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics; D000071676:Zinc Finger Protein GLI1
chemical_list: D000906:Antibodies; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D011994:Recombinant Proteins; C509239:SHH protein, human; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1