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American Journal of Pathology, Vol 143, 753-762, Copyright © 1993 by American Society for Investigative Pathology

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Type 1 plasminogen activator inhibitor gene expression following partial hepatectomy

J Schneiderman, M Sawdey, H Craig, T Thinnes, G Bordin and DJ Loskutoff
Committee for the Study of Vascular Biology, Scripps Research Institute, La Jolla, California 92037.

A murine model of partial hepatectomy (PH) was employed to investigate type 1 plasminogen activator inhibitor (PAI-1) gene expression in regenerating liver. Mice were anesthetized, and a portion of the left lobe of the liver was ligated and resected distal to the ligature, and at various times thereafter, total liver RNA was prepared and analyzed by Northern blotting. PH caused a transient increase in PAI-1 messenger (m)RNA that was apparent within 1 to 2 hours after surgery, was maximal at 8 hours (ninefold increase over sham-operated controls), and then slowly declined. Analysis of discrete liver segments demonstrated much greater induction of PAI-1 mRNA in the region adjacent to PH than in more distal regions. Further analysis of the adjacent tissue by in situ hybridization revealed that PAI-1 mRNA was induced primarily in hepatocytes in the transition zone created by the occluding hemostatic ligature between viable and necrotic tissue. Expression of PAI-1 mRNA could also be detected in this transition zone in capsular mesothelial cells, subcapsular hepatocytes, and venous endothelial cells bordering the area. A much weaker signal was evident in hepatocytes dispersed throughout the remaining intact lobes of PH mice, and no signal was detected in the livers of sham-operated mice. These observations suggest that PAI-1 may be of importance in local tissue remodeling events accompanying liver regeneration.

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