Liver regeneration is transiently impaired in urokinase-deficient mice

被引:50
作者
Roselli, HT
Su, M
Washington, K
Kerins, DM
Vaughan, DE
Russell, WE
机构
[1] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Div Pediat Endocrinol, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA
[3] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA
[4] Vanderbilt Univ, Med Ctr, Dept Pediat & Cell Biol, Nashville, TN 37232 USA
[5] Vet Affairs Med Ctr, Nashville, TN 37232 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 1998年 / 275卷 / 06期
关键词
proteolysis; apoptosis; extracellular matrix; partial hepatectomy; urokinase-type plasminogen activator receptor; DNA synthesis;
D O I
10.1152/ajpgi.1998.275.6.G1472
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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 [H-3]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.
引用
收藏
页码:G1472 / G1479
页数:8
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