Publications [#148573] of Anna Mae Diehl

Papers Published

1. SV Fleig, SS Choi, L Yang, Y Jung, A Omenetti, HM VanDongen, J Huang, JK Sicklick, AM Diehl, Hepatic accumulation of Hedgehog-reactive progenitors increases with severity of fatty liver damage in mice., Laboratory investigation; a journal of technical methods and pathology, vol. 87 no. 12 (December, 2007), pp. 1227-39, ISSN 1530-0307 [doi]
   (last updated on 2013/05/16)

   Abstract:
   Progenitors regenerate fatty livers but the mechanisms involved are uncertain. The Hedgehog pathway regulates mesendodermal progenitors and modulates mesenchymal-epithelial interactions during tissue remodeling. To determine if Hedgehog signaling increases in liver progenitors during fatty liver injury, we compared expression of Hedgehog ligands and target genes across a spectrum of injury. Leptin-deficient ob/ob mice with fatty livers and their healthy lean littermates were studied before and after exposure to the hepatotoxin, ethionine. At baseline, ob/ob mice had greater liver damage than controls. Ethionine induced liver injury in both ob/ob and lean mice, with greater injury occurring in ob/ob mice. After ethionine, the ob/ob mice developed liver atrophy and fibrosis. Liver injury increased hepatic accumulation of progenitors, including ductular cells that produced and responded to Hedgehog ligands. A dose-response relationship was demonstrated between liver injury and expansion of Hedgehog-responsive progenitors. In severely damaged, atrophic livers, nuclei in mature-appearing hepatocytes accumulated the Hedgehog-regulated mesenchymal transcription factor, Gli2 and lost expression of the liver epithelial transcription factor, hepatocyte nuclear factor 6 (HNF-6). Hepatic levels of collagen mRNA and pericellular collagen fibrils increased concomitantly. Hence, fatty liver injury increases Hedgehog activity in liver progenitors, and this might promote epithelial-mesenchymal transitions that result in liver fibrosis.

   Keywords:
   Animals • Drug-Induced Liver Injury • Ethionine • Fatty Liver • Hedgehog Proteins • Hepatocyte Nuclear Factor 6 • Hepatocytes • Kruppel-Like Transcription Factors • Leptin • Ligands • Liver Cirrhosis, Experimental • Male • Mesenchymal Stromal Cells • Mice • Mice, Inbred C57BL • Mice, Obese • Nerve Tissue Proteins • Signal Transduction • chemically induced • etiology • genetics • metabolism • metabolism* • pathology