title: Temporal changes in renal endoglin and TGF-beta1 expression following ureteral obstruction in rats.
abstract: Chronic renal disease is characterized by the accumulation of extracellular matrix proteins in the kidney and a loss of renal function. Tubulointerstitial fibrosis has been reported to play an important role in the progression of chronic renal diseases. Transforming growth factor-beta1 (TGF-beta1) is a profibrotic cytokine playing a major contribution to fibrotic kidney disease. Endoglin is a membrane glycoprotein of the TGF-beta1 receptor system. The aim of this work was to determine the time-course expression of renal type I and IV collagens, endoglin and TGF-beta1 in a rat model of induced tubulointerstitial fibrosis at 1, 3, 10 and 17 days after unilateral ureteral obstruction (UUO). In 17 days-ligated (L)-renal samples, a marked interstitial fibrosis was detected by Masson's trichromic and Sirius red staining, accompanied by an increase in type I collagen expression as shown by immunohistochemical analysis. Northern blot studies revealed a progressive increase in collagen alpha2(I), TGF-beta1 and endoglin mRNA expression in L kidneys when compared with the corresponding non-ligated (NL) kidneys from the animals subjected to left UUO. Seventeen days after UUO, significant increases in collagen alpha2(I), collagen alpha1(IV), TGF-beta1 and endoglin mRNA levels were detected in L kidneys vs NL kidneys. Significantly higher levels of the protein endoglin were found in L kidneys than in NL kidneys 10 and 17 days following obstruction. A marked increase expression for endoglin and TGF-beta1 was localized in renal interstitium by immunohistochemical studies 17 days after obstruction. In conclusion, this work reports the upregulation of endoglin coincident to that of its ligand TGF-beta1 in the kidneys of rats with progressive tubulointerstitial fibrosis induced by UUO.
authors.affiliation: Instituto Reina Sofia de Investigación Nefrológica and Departamento de Fisiología y Farmacología, Salamanca, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Prieto
authors.forename: A B
authors.initials: AB
authors.lastname: Rodríguez-Peña
authors.forename: A
authors.initials: A
authors.lastname: Düwel
authors.forename: J V
authors.initials: JV
authors.lastname: Rivas
authors.forename: N
authors.initials: N
authors.lastname: Docherty
authors.forename: F
authors.initials: F
authors.lastname: Pérez-Barriocanal
authors.forename: M
authors.initials: M
authors.lastname: Arévalo
authors.forename: C P H
authors.initials: CP
authors.lastname: Vary
authors.forename: C
authors.initials: C
authors.lastname: Bernabeu
authors.forename: J M
authors.initials: JM
authors.lastname: López-Novoa
authors.forename: N
authors.initials: N
authors.lastname: Eleno
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism; D000071063:Endoglin; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D014517:Ureteral Obstruction
chemical_list: D024042:Collagen Type I; D024141:Collagen Type IV; D000071063:Endoglin; C501740:Eng protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1