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


CONCLUSIONS
Our study indicated that CTGF and TGF-beta may play an important role in glomerular histopathologic change in DN.
Umezono
Tomoya
T
Division of Nephrology and Metabolism, Department of Internal Medicine, Tokai University, School of Medicine, Kanagawa, Japan. umechan@is.icc.u-tokai.ac.jp
Toyoda
Masao
M
Kato
Mayuko
M
Miyauchi
Masaaki
M
Kimura
Moritugu
M
Maruyama
Mayumi
M
Honma
Masashi
M
Yagame
Mitsunori
M
Suzuki
Daisuke
D
D000328:Adult; D024141:Collagen Type IV / Q000096:biosynthesis*; D055513:Connective Tissue Growth Factor; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005920:Glomerular Mesangium / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis*; D017403:In Situ Hybridization / Q000379:methods; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology; D012261:Ribonucleoproteins / Q000096:biosynthesis; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis*
C526317:CCN2 protein, human; D024141:Collagen Type IV; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012261:Ribonucleoproteins; D053773:Transforming Growth Factor beta1; C026452:messenger ribonucleoprotein; D055513:Connective Tissue Growth Factor