Changes in beta(1) integrin in renal tubular epithelial cells after intrauterine asphyxia of rabbit pups.
OBJECTIVE
We investigated the role of beta(1) integrin in acute renal tubular injury caused by intrauterine asphyxia of neonatal rabbits by exploring the distribution and expression changes in beta(1) integrin and its mRNA in renal tubular epithelial cells.


METHODS
A catheter was used to temporarily block the abdominal aortas of New Zealand pregnant rabbits in order to set up the intrauterine asphyxia animal model. The rabbit pups were randomly divided into control, asphyxia, and calpain inhibitor intervention groups and their renal tubular tissues were examined at 2 h after asphyxia. Immunofluorescence and in situ hybridization were used to examine the expression of beta(1) integrin and its mRNA, respectively. Western blot analysis was used to show the proteolysis of beta(1) integrin. Calpain inhibitor I was used to show the protective effect of keeping beta(1) integrin from being hydrolyzed after asphyxia.


RESULTS
(1) Normally, beta(1) integrin was located exclusively at the basal surface of renal tubular epithelial cells. After asphyxia a large amount of beta(1) integrin shifted from the basal surface to the cytoplasma and the lateral and apical surfaces and its expression decreased significantly, with simultaneous damage to renal tubular integrity and structure, many exfoliated cells and cell fragments obstructed the tubular lumen. (2) The mRNA of beta(1) integrin was mainly expressed in the cytoplasma. After asphyxia its expression increased significantly. (3) Proteolysis of beta(1) integrin was evident after asphyxia, but was significantly reduced in the calpain inhibitor intervention group. Calpain inhibitor I prevented the decrease and dislocation of beta(1) integrin and protected renal tubular integrity and structure.


CONCLUSIONS
Intrauterine asphyxia caused proteolysis of beta(1) integrin, with reduced expression and depolarized distribution, leading to tubular lumen obstruction and renal tubule destruction. Damage to beta(1) integrin and the renal tubule was related to the activation of calpain, and calpain inhibitor curtailed these effects.
Yu
Bo
B
Department of Neonatology, The 2nd Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang, China. dog4317169@hotmail.com
Li
Shasha
S
Yao
Yujia
Y
Lin
Zhenlang
Z