CRBP-I in the renal tubulointerstitial compartment of healthy rats and rats with renal fibrosis

CRBP-I IN THE RENAL TUBULOINTERSTITIAL COMPARTMENT OF HEALTHY RATS AND RATS WITH RENAL FIBROSIS.
Katrien Van Beneden (1), Caroline Geers (2), Marina Pauwels (1), Alexis Desmoulière (3), Leo A. van Grunsven (4), Dierik Verbeelen (5), Albert Geerts (4) and Christiane Van den Branden (1)
1: Department of Human Anatomy, Vrije Universiteit Brussel, Brussels
2: Department of Pathology, Universitair Ziekenhuis Brussel, Brussels
3: Faculty of Pharmacy, Université de Limoges, Limoges, France
4: Department of Cell Biology, Vrije Universiteit Brussel, Brussels
5: Department of Nephrology, Universitair Ziekenhuis Brussel, Brussels
Cellular retinol binding protein-I (CRBP-I), a member of the intracellular lipid binding protein (iLBP) superfamily, is a specific marker of quiescent stellate cells in healthy human liver. In diseased fibrotic/cirrhotic liver, stellate cells remain CRBP-I positive, in addition, portal and septal myofibroblasts acquire CRBP-I expression (1). Here we investigate the distribution of CRBP-I in the renal cortex of healthy rats and rats with renal fibrosis. To induce chronic renal failure with glomerulosclerosis and tubulointerstitial fibrosis we used the adriamycin model of nephropathy. Kidneys of healthy and adriamycin-treated rats were studied by immunohistochemistry, using antibodies against CRBP-I, desmin and vimentin. Double stainings were done with immunofluorescence to identify the cell type expressing CRBP-I in the renal interstitium. The tubulointerstitial compartment of healthy and adriamycin-induced fibrotic rat kidney was isolated and Western blotting was performed to semi-quantify the expression levels of vimentin, desmin, alpha-smooth muscle actin and CRBP-I. In normal rat kidney, the convoluted proximal tubular epithelial cells express CRBP-I, no CRBP-I expression is found in the interstitium, nor in the glomeruli (2,3). In adriamycin-induced fibrotic rat kidney, CRBP-I expression diminishes in the convoluted proximal tubular epithelial cells, whereas a distinct subpopulation of peritubular myofibroblasts in the renal interstitium (70% ± 3%) acquires CRBP-I expression, co-expressing desmin.
We conclude that in the tubulointerstitial compartment of adriamycin-induced fibrotic rat kidney, CRBP-I is expressed in a different pattern than in healthy rat kidney. As the convoluted proximal tubular epithelial cells dedifferentiate during fibrosis, CRBP-I expression decreases and de novo expression of CRBP-I is found in activated myofibroblast-like cells in the renal interstitium of adriamycin-treated rats, indicating a similar CRBP-I expression as in fibrotic or cirrhotic liver (1). Therefore, CRBP-I can be considered as a good marker for renal interstitial fibrosis, interestingly, CRBP-I expression is present in a distinct subpopulation of myofibroblastic cells.
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