Temporal changes in renal endoglin and TGF-alfa1 expression following ureteral obstruction in rats

ABSTRACT

Chronic renal disease is characterized by the accumulation of extracellular matrixproteins in the kidney and a loss of renal function. Tubulointerstitial fibrosis hasbeen reported to play an important role in the progression of chronic renal diseases.Transforming growth factor-beta1 (TGF-alpha1) is a profibrotic cytokine playing amajor contribution to fibrotic kidney disease. Endoglin is a membrane glycoproteinof the TGF-alpha1 receptor system. The aim of this work was to determine the timecourseexpression of renal type I and IV collagens, endoglin and TGF-alpha1 in a ratmodel of induced tubulointerstitial fibrosis at 1, 3, 10 and 17 days after unilateralureteral obstruction (UUO). In 17 days-ligated (L)-renal samples, a marked interstitialfibrosis was detected by Masson’s trichromic and Sirius red staining, accompaniedby an increase in type I collagen expression as shown by immunohistochemicalanalysis. Northern blot studies revealed a progressive increase in collagen alpha2(I),TGF-alpha1 and endoglin mRNA expression in L kidneys when compared with the correspondingnon-ligated (NL) kidneys from the animals subjected to left UUO. Seventeendays after UUO, significant increases in collagen alpha2(I), collagen alpha1(IV),TGF-alpha1 and endoglin mRNA levels were detected in L kidneys vs NL kidneys. Significantlyhigher levels of the protein endoglin were found in L kidneys than in NLkidneys 10 and 17 days following obstruction. A marked increase expression forendoglin and TGF-alpha1 was localized in renal interstitium by immunohistochemical studies 17 days after obstruction. In conclusion, this work reports the upregulationof endoglin coincident to that of its ligand TGF-alpha1 in the kidneys of rats with progressivetubulointerstitial fibrosis induced by UUO (AU)

RESUMEN

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