CYCLOSPORINE INDUCES ELEVATED PROCOLLAGEN ALPHA-1 (I) MESSENGER-RNA LEVELS IN THE RAT RENAL-CORTEX

Chronic cyclosporine nephrotoxicity is a poorly understood drug side-effect characterized by renal cortical interstitial scarring. To evaluate procollagen mRNA levels as an early factor in the development of this form of renal fibrosis, we measured renal procollagen alpha 1 (I), alpha 1 (III), alpha 1 (IV) and beta-actin mRNA levels in rats treated with cyclosporine (CsA) or the olive oil vehicle (OO) for one or four weeks. Renal morphology was similar without atrophy or fibrosis in one week CsA and OO and four week OO rats. Four week CsA rats had focal cortical interstitial fibrosis and tubular atrophy. Cortical procollagen alpha 1 (I) mRNA levels were increased in CsA versus OO rats at one week (P < 0.02) and four weeks (P < 0.02). One week medullary procollagen alpha 1 (I) and all other one week medullary, and one and four week cortical procollagen and beta-actin mRNA levels were no different in CsA versus OO rats. The early increase in renal cortical procollagen alpha 1 (I) mRNA levels precedes renal morphologic abnormalities, and may represent an important step in the pathogenesis of cyclosporine-induced renal cortical fibrosis.