Extracellular matrix in fetal kidney after experimental obstruction.
OBJECTIVE
We studied the long-term effects of complete unilateral ureteral obstruction on the extracellular matrix composition of the fetal kidney interstitium in neonatal opossums.


METHODS
We created complete left ureteral obstruction in 2-week-old opossum pups. Sham operated animals served as controls. A total of 12 animals were sacrificed 2, 3 and 5 weeks after obstruction, and the kidneys were harvested. Resultant tissue sections were prepared for light and electron microscopy, and immunohistochemical testing for alpha-smooth muscle action (SMA), fibronectin, laminin and type IV collagen. In situ hybridization was done to determine interstitial collagen type I. Western blot analysis was performed on single kidney protein extracts for alpha-SMA, fibronectin and laminin.


RESULTS
Light microscopy revealed established interstitial fibrosis and tubular atrophy 2 weeks after obstruction which increased with the duration of obstruction. Electron microscopy showed an increased number of interstitial fibroblasts, increased extracellular lucent substance and thin collagen fibrils. The tubular basement membranes were irregular and thickened compared with the continuous and even contours in controls. The deposition of alpha-SMA, fibronectin, collagen types I and type IV were markedly increased in the interstitium compared with controls and were highest at 5 weeks. Type IV collagen was associated with aberrant peritubular capillaries within the scarred interstitium. There were no appreciable differences in laminin expression in obstructed and sham operated kidneys.


CONCLUSIONS
Experimental obstruction in opossums alters the cell phenotype, extracellular matrix and microcapillary composition in the fetal kidney interstitium. Biosynthetic properties of the interstitial fibroblasts in obstructed kidneys appear similar to those of undifferentiated mesenchyma before the induction of nephrons. We propose that these aberrant extracellular matrices coincident with cytoarchitectural disturbance may form a faulty scaffold that hampers normal kidney development secondary to complete unilateral ureteral obstruction.
Liapis
H
H
Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri, USA.
Barent
B
B
Steinhardt
G F
GF
D000818:Animals; D000831:Animals, Newborn; D005109:Extracellular Matrix; D007668:Kidney / Q000196:embryology* / Q000473:pathology*; D009893:Opossums; D014517:Ureteral Obstruction / Q000378:metabolism*