title: Progression of microalbuminuria in SHR is associated with lower expression of critical components of the apical endocytic machinery in the renal proximal tubule.
abstract: Cumulative epidemiological evidence indicates that the presence of microalbuminuria predicts a higher frequency of cardiovascular events, peripheral disease, and mortality in essential hypertension. Microalbuminuria may arise from increased glomerular permeability and/or reduced proximal tubular reabsorption of albumin by receptor-mediated endocytosis. This study aimed to evaluate the temporal pattern of urinary protein excretion and to test the hypothesis that progression of microalbuminuria is associated with decreased protein expression of critical components of the endocytic apparatus in the renal proximal tubule of spontaneously hypertensive rats (SHR). We found that urinary albumin excretion increased progressively with blood pressure in SHR from 6 to 21 wk of age. In addition, SDS-PAGE analysis of urinary proteins showed that microalbuminuric SHR virtually excreted proteins of the size of albumin or smaller (<70 kDa), typical of tubular proteinuria. Moreover, the protein abundance of the endocytic receptors megalin and cubilin as well as of the chloride channel ClC-5 progressively decreased in the renal cortex of SHR from 6 to 21 wk of age. Expression of the vacuolar H⁺-ATPase B2 subunit was also reduced in the renal cortex of 21-wk-old compared with both 6- and 14-wk-old SHR. Collectively, our study suggests that enhanced urinary protein excretion, especially of albumin, may be due, at least in part, to lower expression of key components of the apical endocytic apparatus in the renal proximal tubule. Finally, one may speculate that dysfunction of the apical endocytic pathway in the renal proximal tubule may contribute to the development of microalbuminuria in essential hypertension.
authors: Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.
authors: Bruna H
authors: BH
authors: Inoue
authors: Daniel F
authors: DF
authors: Arruda-Junior
authors: Luciene C G
authors: LC
authors: Campos
authors: Ana Luiza T
authors: AL
authors: Barreto
authors: Mariliza V
authors: MV
authors: Rodrigues
authors: José Eduardo
authors: JE
authors: Krieger
authors: Adriana C C
authors: AC
authors: Girardi
mesh_terms: D000419:Albuminuria / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001794:Blood Pressure; D018450:Disease Progression; D004705:Endocytosis; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000378:metabolism; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism
chemical_list: D026561:Low Density Lipoprotein Receptor-Related Protein-2; D011956:Receptors, Cell Surface; D014168:Transferrin; C029486:intrinsic factor-cobalamin receptor
keywords: ClC-5; cubilin; hypertension; megalin; receptor-mediated endocytosis; vacuolar H+-ATPase