INCREASED EXPRESSION OF DECORIN IN EXPERIMENTAL HYDRONEPHROSIS

Transforming growth factor (TGF)-beta 1 is a potential mediator of tub ulointerstitial (TI) fibrosis in the rat unilateral ureteral obstructi on (UUO) model. Decorin is a protein composed of a core protein and a chondroitin sulfate side chain and is capable of inactivating TGF-beta . Since TGF-beta strongly induces the synthesis of decorin in experime ntal glomerulonephritis, it was our intent to investigate whether alte red decorin expression is operant in the rat UUO model. Renal cortical decorin mRNA levels initially became elevated (2.5-fold) in obstructe d kidney (OBK) versus contralateral unobstructed kidney (CUK) 24 hours post-UUO and remained greater in the OBK specimens at 48 (2.3-fold), 96 (2.2-fold), and 168 (1.9-fold) hours post-ureteral ligation. Whole- body X-irradiation 11 days prior to UUO significantly reduced decorin mRNA at 24 and 96 hours post-UUO. On immunolabeling, decorin was only evident in the adventitia of blood vessels in CUK specimens at any tim e point after UUO. In contrast, OBK specimens initially demonstrated p eriglomerular and peritubular interstitial localization of decorin at 96 hours post-ureteral ligation, which became even more intense and di ffuse in the tubulointerstitium at 168 hours post-UUO. On Western anal ysis, there were highly significant increases in decorin protein expre ssion in the OBK versus the CUK specimens al 96 and 168 hours post-UUO . Levels of active TGF-beta 1 in the renal cortex of OBK were 1.9- and 3.6-fold higher than CUK at 48 and 96 hours post-UUO. In summary, we demonstrated that post-UUO, decorin mRNA and protein expression is up- regulated in the renal cortex of OBK, but not CUK, specimens in a temp oral parallel with active TGF-beta 1 levels and macrophage infiltratio n. We postulate that the development of TI fibrosis in this model may be related to only a physiologic induction of decorin by TGF-beta, and that pharmacologic levels may be required to retard or prevent scarri ng via TGF-beta inhibition.