MAST-CELLS AND TYPE-VIII COLLAGEN IN HUMAN DIABETIC NEPHROPATHY

Renal injury in diabetes mellitus is associated with progressive inter stitial fibrosis and extracellular matrix accumulation. However, the p henotypes of cells forming the interstitial infiltrate in diabetic nep hropathy have not been precisely defined. There is increasing evidence for the association of mast cells with angiogenesis, chronic inflamma tory conditions and fibrosis. We have recently shown that human mast c ells can produce the non-fibrillar short chain type VIII collagen in v ivo. Using immunohistochemistry, in situ hybridisation and reverse tra nscriptase-polymerase chain reaction, we examined the contribution of mast cells and type VIII collagen to the fibrotic changes occurring in biopsy-proven diabetic nephropathy. We observed that the number of in terstitial mast cells was significantly increased in diabetic nephropa thy compared with normal kidney tissue. In specimens from diabetic sub jects, intense immunohistochemical staining for type VIII collagen was detected in mast cells, on periglomerular fibres and in perivascular and interstitial sites. The expression of type VIII collagen in perigl omerular and interstitial sites coincided with that of alpha smooth mu scle actin, a marker for myofibroblastic differentiation. mRNA for typ e VIII collagen was detected by reverse transcriptase-polymerase chain reaction in diabetic nephropathy and in a human mast cell line. By in situ hybridisation the transcripts or type VIII collagen were localis ed to renal mast cells. The increased number of mast cells and the ele vated type VIII collagen deposition in human diabetic nephropathy prov ides a potential link between the extracellular matrix accumulation an d the fibrosis observed in this condition.