Clinical Investigation

Kidney International (1994) 46, 1368–1374; doi:10.1038/ki.1994.406

Tubular basement membrane changes during induction and regression of drug-induced polycystic kidney disease

Frank A Carone, Ralph J Butkowski, Sakie Nakamura, Momir Polenakovic caron and Yashpal S Kanwar

Department of Pathology, Northwestern University Medical School, Chicago, Illinois, and Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA, and Department of Nephrology, Faculty of Medicine, Skopje, Macedonia

Correspondence: Frank Carone MD, Department of Pathology, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, Illinois 60611-3008, USA.

Received 28 February 1994; Revised 15 June 1994; Accepted 16 June 1994.

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Abstract

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 Mr ~ 380,000, 250,000 and 145,000, and a decrease in the component with Mr ~ 55,000. Immunoblot analyses revealed that the major components of TBM (type-IV collagen, laminin beta1 and beta2 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. Since cell-matrix integrity is vital in the maintenance of normal biophysiology of the renal tubule, the observed altered expressions in various ECM glycoproteins may be relevant to the pathogenetic mechanisms involved in the development and progression of PKD.

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