Premium
Focal increases in hyaluronan and CD44 correlate with high proliferative activity and fibrosis in nephrotoxic‐induced chronic renal failure (CRF)
Author(s) -
Decleves AnneEmilie,
Lorfevre Francois,
clercq Denis,
Toubeau Gerard,
Caron Nathalie,
Flamion Bruno
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a342-c
Subject(s) - cd44 , chronic renal failure , medicine , nephrotoxicity , fibrosis , endocrinology , pathology , kidney , chemistry , biochemistry , cell
CRF involves heterogeneous alterations in the nephrons and increased proliferative activity associated with tubular regeneration and interstitial fibrosis. This picture may not be mimicked by remnant kidney models. We administered nephrotoxic agents (K 2 Cr 2 O 7 + HgCl 2 ) by single sc injection to Wistar rats. Surviving animals developed CRF with atrophic and hypertrophic changes in the nephrons. Histological sections taken between 1 wk and 6 months post‐injection were examined for tissue injury, tubular and interstitial cell proliferation, immunostaining of hyaluronan (HA) and its main receptor CD44, and fibrosis. One week after injury, tubular damage and regeneration associated with large deposits of HA and abundant inflammatory cells in the peritubular matrix. CD44 was expressed in both lymphocytes and macrophages, and in undifferentiated, regenerative epithelial cells. At longer term, some altered proximal tubules regained a differentiated phenotype while progressively losing CD44. Peritubular HA declined in parallel to recovering tubules. Strikingly, however, strong HA reactivity was retained in areas of chronic tubular alterations, together with CD44 in cystic and atrophic tubules, focal proliferation of interstitial cells, and patchy fibrosis. Our data obtained in a realistic model of CRF suggest that HA and CD44 are involved in the proliferation of both tubular regenerative cells and interstitial cells, the latter associated with patches of progressive fibrosis. Supported by Belgian National Fund for Scientific Research (FNRS).