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1 St. Helier Hospital, SW Thames Institute for Renal Research, Carshalton, United Kingdom
2 Leicester General Hospital, Department of Nephrology, Leicester, Leicestershire, United Kingdom
* To whom correspondence should be addressed. E-mail: ramaswamy.diwakar{at}gmail.com.
Proteinuria predicts the decline of renal function in chronic kidney disease. Reducing albuminuria has been shown to be associated with a reduction in this rate of decline. PTECs, when exposed to albumin produce matrix proteins, pro-inflammatory and pro-fibrotic cytokines like TGF
-1. Some of these effects are dependent on endocytosis of albumin by PTECs. However conditions like diabetic nephropathy, believed to be associated with reduced albumin endocytosis are associated with interstitial fibrosis. Moreover, megalin the putative albumin binding receptor in PTECs has potential signalling motifs in its cytoplasmic domain suggesting its ability to signal in response to ligand binding from the apical surface of PTECs. Hence we looked to see whether albumin induced secretion of TGF-1 by PTECs is dependent on albumin endocytosis or if it could occur in the absence of albumin endocytosis. We studied the production of TGF-1 in two accepted models of PTECs, Opossum kidney (OK) cells and HKC-8 cells, with widely varying degrees of endocytosis. We then studied the effect of inhibiting albumin endocytosis with various inhibitors on albumin induced TGF-1 secretion. Our results indicate that albumin induced TGF-1 secretion by PTECs does not require albumin endocytosis and therefore the mechanism for the induction of some pro-fibrotic responses by albumin may differ from those required for some of the inflammatory responses. Moreover, we found that albumin induced TGF-1 secretion by PTECs is not dependent on its interaction with megalin.
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