Morphology of liver repair following cholestatic liver injury: Resolution of ductal hyperplasia, matrix deposition and regression of myofibroblasts

Ramm, G. A., Carr, S. C., Bridle, K. R., Li, L., Britton, R. S., Crawford, D. H. G., Vogler, C. A., Bacon, B. R. and Tracy, T. F. (2000) Morphology of liver repair following cholestatic liver injury: Resolution of ductal hyperplasia, matrix deposition and regression of myofibroblasts. Liver, 20 5: 387-396. doi:10.1034/j.1600-0676.2000.020005387.x


Author Ramm, G. A.
Carr, S. C.
Bridle, K. R.
Li, L.
Britton, R. S.
Crawford, D. H. G.
Vogler, C. A.
Bacon, B. R.
Tracy, T. F.
Title Morphology of liver repair following cholestatic liver injury: Resolution of ductal hyperplasia, matrix deposition and regression of myofibroblasts
Journal name Liver   Check publisher's open access policy
ISSN 0106-9543
Publication date 2000-10
Sub-type Article (original research)
DOI 10.1034/j.1600-0676.2000.020005387.x
Volume 20
Issue 5
Start page 387
End page 396
Total pages 10
Place of publication Malden, MA, United States
Publisher Wiley-Blackwell
Language eng
Formatted abstract
Background/Aims: Myofibroblasts are the primary cells responsible for increased matrix deposition in hepatic fibrosis. Activation of hepatic stellate cells and portal fibroblasts to myofibroblasts during cholestatic liver injury is acompanied by increased expression of the activation marker, α-smooth muscle actin (SMA), and collagen genes. In contrast to our understanding of injury, the cellular mechanisms of liver repair are not well defined. This study was designed to examine the morphological relationship between bile duct hyperplasia, matrix deposition and myofibroblast phenotype in a model of chronic cholestatic liver injury and repair.

Methods: Reversible extrahepatic obstruction was accomplished in rats using a soft vessel loop suspended from the anterior abdominal wall: duct manipulation alone was performed in sham-operated controls. After 7 days, rats were either sacrificed or decompressed by release of the loop and subsequently sacrificed 2-10 days after reversal. Liver sections were obtained for in situ hybridization for procollagen α1(I) mRNA, immunohistochemical staining for SMA and cytokeratin 19, and histochemical staining for reticulin.

Results: Cholestatic livers demonstrated bile duct hyperplasia, which reversed to normal within 10 days after decompression. Fibrosis was also substantially reduced during this period. SMA-positive myofibroblasts were abundant and localized to regions adjacent to proliferating ducts and excess matrix in the obstructed animals. Decompressed livers showed a dramatic time-dependent reduction in the number of SMA-positive cells and in the expression of procollagen I mRNA.

Conclusions: Our results show that the disappearance of bile duct hyperplasia after biliary decompression is accompanied by a similarly rapid loss of SMA-positive myofibroblasts. Both cellular events may abrogate enhanced matrix synthesis and allow repair to occur.
Keyword Collagen
Cytokeratin 19
Hepatic fibrosis
Hepatic stellate cells
Smooth muscle actin
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Wed, 09 Mar 2011, 15:49:48 EST