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Am J Physiol Gastrointest Liver Physiol 275: G1472-G1479, 1998;
0193-1857/98 $5.00
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Vol. 275, Issue 6, G1472-G1479, December 1998

Liver regeneration is transiently impaired in urokinase-deficient mice

Heather T. Roselli1, Ming Su2, Kay Washington3, David M. Kerins2, Douglas E. Vaughan1,2, and William E. Russell4

Departments of 1 Pharmacology, 2 Medicine, 3 Pathology, and 4 Pediatrics and Cell Biology, Vanderbilt University Medical Center and Veterans Affairs Medical Center, Nashville, Tennessee 37232

To test the hypothesis that urokinase-type plasminogen activator (uPA) plays an important role in liver regeneration in vivo, partial hepatectomy was performed on wild-type and uPA-deficient (uPA-/-) mice. Mice were studied at 24, 44, and 96 h and at 8 days and 4 wk post-partial hepatectomy for evidence of regeneration, as measured by mitotic indexes and [3H]thymidine incorporation. In wild-type mice, thymidine incorporation peaked at 44 h and this index was reduced by 47% in uPA-/- mice (P = 0.02). By 8 days, however, liver mass was comparable in both groups. Histological analysis revealed the presence of focal areas of fibrin deposition and cellular loss by 24 h that were more severe and prevalent in uPA-/- mice than in wild-type mice (62 and 23%, respectively; chi 2 = 3.939, P = 0.047). In contrast, regeneration was not impaired in uPA receptor (uPAR)-deficient mice at 24 and 44 h. Taken together, these data indicate that uPA, independent of its interaction with the uPAR, plays an important role in liver regeneration in vivo.

proteolysis; apoptosis; extracellular matrix; partial hepatectomy; urokinase-type plasminogen activator receptor; DNA synthesis


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