J. Schneiderman et al., TYPE-1 PLASMINOGEN-ACTIVATOR INHIBITOR GENE-EXPRESSION FOLLOWING PARTIAL-HEPATECTOMY, The American journal of pathology, 143(3), 1993, pp. 753-762
A murine model of partial hepatectomy (PH) was employed to investigate
type 1 plasminogen activator inhibitor (PAI-1) gene expression in reg
enerating liver. Mice were anesthetized, and a portion of the left lob
e of the liver was ligated and resected distal to the ligature, and at
various times thereafter, total liver RNA was prepared and analyzed b
y Northern blotting. PH caused a transient increase in PAI-1 messenger
(m)RNA that was apparent within 1 to 2 hours after surgery, was maxim
al at 8 hours (ninefold increase over sham-operated controls), and the
n slowly declined. Analysis of discrete liver segments demonstrated mu
ch greater induction of PAI-1 mRNA in the region adjacent to PH than i
n more distal regions. Further analysis of the adjacent tissue by in s
itu hybridization revealed that PAI-1 mRNA was induced primarily in he
patocytes in the transition zone created by the occluding hemostatic l
igature between viable and necrotic tissue. Expression of PAI-1 mRNA c
ould 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 t
hroughout the remaining intact lobes of PH mice, and no signal was det
ected in the livers of sham-operated mice. These observations suggest
that PAI-1 may be of importance in local tissue remodeling events acco
mpanying liver regeneration.