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Bile ductules and stromal cells express hedgehog ligands and/or hedgehog target genes in primary biliary cirrhosis.
Hepatology. 2007 May; 45(5):1091-6.Hep

Abstract

Indian Hedgehog (Ihh) regulates tissue morphogenesis. Hedgehog (Hh) activity has been demonstrated in human cholangiocarcinoma and hepatocellular carcinoma lines, and in myofibroblasts and progenitors from adult rodent livers. We evaluated Hh pathway involvement in the response to biliary injury in primary biliary cirrhosis (PBC). Liver sections from 3 PBC patients and 3 controls without liver disease were studied. Immunohistochemistry was used to determine if cells that accumulate in PBC livers express Ihh or Hh-target genes including the Hh-receptor, Patched (Ptc), and the Hh-transcriptional activator glioblastoma (Gli) 2. Positive cells were further identified by costaining for cytokeratin (CK) 19, a biliary marker, or OV6, a hepatic progenitor marker. In all subjects, Gli2 and Ptc expression localized in portal areas. The numbers of Gli2- or Ptc-expressing cells/portal triad were each 10-fold greater in patients with PBC than in controls (P<0.05). In PBC livers, some CK19+ cells coexpressed Gli2 or Ptc. Many stromal fibroblastic cells were also Gli2+. Strong Ihh expression was detected in most bile ductular cells. Scattered stromal cells also expressed Ihh. The number of Ihh+ cells/portal triad was 6-fold greater in PBC livers than controls (P<0.05). OV6+ progenitors increased significantly in PBC livers, and some of these cells coexpressed Ihh, Ptc, and/or Gli2.

CONCLUSION

This is the first direct evidence that noncancerous, adult human livers harbor several types of cells that produce and/or respond to Hh ligands. Such Hh-responsive cells accumulate during the fibroproliferative response to chronic cholestatic liver injury, suggesting a role for Hh signaling in this process.

Authors+Show Affiliations

Division of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17464985

Citation

Jung, Youngmi, et al. "Bile Ductules and Stromal Cells Express Hedgehog Ligands And/or Hedgehog Target Genes in Primary Biliary Cirrhosis." Hepatology (Baltimore, Md.), vol. 45, no. 5, 2007, pp. 1091-6.
Jung Y, McCall SJ, Li YX, et al. Bile ductules and stromal cells express hedgehog ligands and/or hedgehog target genes in primary biliary cirrhosis. Hepatology. 2007;45(5):1091-6.
Jung, Y., McCall, S. J., Li, Y. X., & Diehl, A. M. (2007). Bile ductules and stromal cells express hedgehog ligands and/or hedgehog target genes in primary biliary cirrhosis. Hepatology (Baltimore, Md.), 45(5), 1091-6.
Jung Y, et al. Bile Ductules and Stromal Cells Express Hedgehog Ligands And/or Hedgehog Target Genes in Primary Biliary Cirrhosis. Hepatology. 2007;45(5):1091-6. PubMed PMID: 17464985.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bile ductules and stromal cells express hedgehog ligands and/or hedgehog target genes in primary biliary cirrhosis. AU - Jung,Youngmi, AU - McCall,Shannon J, AU - Li,Yin-Xiong, AU - Diehl,Anna Mae, PY - 2007/4/28/pubmed PY - 2007/5/26/medline PY - 2007/4/28/entrez SP - 1091 EP - 6 JF - Hepatology (Baltimore, Md.) JO - Hepatology VL - 45 IS - 5 N2 - UNLABELLED: Indian Hedgehog (Ihh) regulates tissue morphogenesis. Hedgehog (Hh) activity has been demonstrated in human cholangiocarcinoma and hepatocellular carcinoma lines, and in myofibroblasts and progenitors from adult rodent livers. We evaluated Hh pathway involvement in the response to biliary injury in primary biliary cirrhosis (PBC). Liver sections from 3 PBC patients and 3 controls without liver disease were studied. Immunohistochemistry was used to determine if cells that accumulate in PBC livers express Ihh or Hh-target genes including the Hh-receptor, Patched (Ptc), and the Hh-transcriptional activator glioblastoma (Gli) 2. Positive cells were further identified by costaining for cytokeratin (CK) 19, a biliary marker, or OV6, a hepatic progenitor marker. In all subjects, Gli2 and Ptc expression localized in portal areas. The numbers of Gli2- or Ptc-expressing cells/portal triad were each 10-fold greater in patients with PBC than in controls (P<0.05). In PBC livers, some CK19+ cells coexpressed Gli2 or Ptc. Many stromal fibroblastic cells were also Gli2+. Strong Ihh expression was detected in most bile ductular cells. Scattered stromal cells also expressed Ihh. The number of Ihh+ cells/portal triad was 6-fold greater in PBC livers than controls (P<0.05). OV6+ progenitors increased significantly in PBC livers, and some of these cells coexpressed Ihh, Ptc, and/or Gli2. CONCLUSION: This is the first direct evidence that noncancerous, adult human livers harbor several types of cells that produce and/or respond to Hh ligands. Such Hh-responsive cells accumulate during the fibroproliferative response to chronic cholestatic liver injury, suggesting a role for Hh signaling in this process. SN - 0270-9139 UR - https://www.unboundmedicine.com/medline/citation/17464985/Bile_ductules_and_stromal_cells_express_hedgehog_ligands_and/or_hedgehog_target_genes_in_primary_biliary_cirrhosis_ L2 - https://doi.org/10.1002/hep.21660 DB - PRIME DP - Unbound Medicine ER -