Glomerular expression of CTGF, TGF-beta 1 and type IV collagen in diabetic nephropathy.

摘要

Background: In development of progressive extracellular matrix accumulation, connective tissue growth factor (CTGF) may act as a downstream mediator of transforming growth factor-beta 1 (TGF-beta 1). However, the association and the correlation of these cytokines and extracellular matrix accumulation in human diabetic nephropathy (DN) is not fully understood. Methods: To explore the possible involvement of TGF-beta 1 and CTGF in extracellular matrix accumulation in DN, high-resolution in situ hybridization with digoxigenin-labeled antisense oligonucleotides to CTGF, TGF-beta 1 and type IV collagen mRNAs were performed in DN and in histologically normal human kidney (NHK). To quantify expression of each mRNA, the fraction of all nuclear cells that were positively stained in the cytoplasm was determined in at least 10 randomly selected cross-sections of nonsclerotic glomeruli. Results: Both in DN and in NHK, CTGF, TGF-beta 1 and type IV collagen mRNAs were mainly expressed by glomerular mesangial, visceral epithelial and parietal epithelial cells. The percentages of positive glomerular resident cells were significantly higher for each mRNA in DN compared with NHK. Especially, the expression of CTGF mRNA was also notably increased in case of DN with only mild histopathologic lesions. The extent of expression of each mRNA was significantly correlated to that of each other mRNA examined. Conclusion: Our study indicated that CTGF and TGF-beta may play an important role in glomerular histopathologic change in DN.