Tubular basement membrane changes during induction and regression of drug-induced polycystic kidney disease.
Defective cell-extracellular matrix (ECM) biophysiology is considered a factor in the development of polycystic kidney disease (PKD). Altered biosynthesis of various ECM components may result in tubular dysmorphogenesis and uncontrolled tubular cystic expansion. In this study, expression of certain ECM components was investigated in a diphenylthiazole (DPT)-induced rat model of PKD. DPT induces cystic change in all the collecting tubules, most severe in the outer medulla and inner cortex, and following withdrawal of DPT, cystic tubules return to normal with persistence of focal interstitial fibrosis. SDS-PAGE analyses of isolated tubular basement membranes (TBMs) of control and PKD kidneys revealed overall similar electrophoretic migratory bands. However, in PKD, there were relative increases in components with M(r) approximately 380,000, 250,000 and 145,000, and a decrease in the component with M(r) approximately 55,000. Immunoblot analyses revealed that the major components of TBM (type-IV collagen, laminin beta 1 and beta 2 chains and entactin) were present in the same relative concentrations in control and PKD. The expression of tubulointerstitial (TIN) antigen was decreased. Also, the relative concentrations of type-I collagen and fibronectin were increased in the PKD group. Following recovery, the expressions of TIN and fibronectin returned to normal, whereas type-I collagen remained elevated. ELISA determinations revealed increased expression of interstitial collagens type-I, -V and -VI in PKD vs control and they remained elevated following recovery, while that of type-III was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pathology, Northwestern University Medical School, Chicago, Illinois.
F A
FA
Carone
R J
RJ
Butkowski
S
S
Nakamura
M
M
Polenakovic
Y S
YS
Kanwar
D000818:Animals; D001485:Basement Membrane / Q000378:metabolism / Q000473:pathology; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D007672:Kidney Cortex / Q000378:metabolism / Q000473:pathology; D007679:Kidney Medulla / Q000378:metabolism / Q000473:pathology; D007685:Kidney Tubules, Collecting / Q000378:metabolism* / Q000473:pathology; D007690:Polycystic Kidney Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D013844:Thiazoles
D016326:Extracellular Matrix Proteins; D013844:Thiazoles