In situ expression of connective tissue growth factor in human crescentic glomerulonephritis.
Connective tissue growth factor (CTGF) has recently been recognized as an important profibrotic factor and is up-regulated in various renal diseases with fibrosis. The present study describes the sequential localization of CTGF mRNA and its association with transforming growth factor (TGF)-beta1 in human crescentic glomerulonephritis (CRGN). Furthermore, we examined the phenotype of CTGF-expressing cells using serial section analysis. Kidney biopsy specimens from 18 CRGN patients were examined using in situ hybridization and immunohistochemistry. CTGF mRNA was expressed in the podocytes and parietal epithelial cells (PECs) in unaffected glomeruli. In addition, it was strongly expressed in the cellular and fibrocellular crescents, particularly in pseudotubule structures. Serial sections revealed that the majority of CTGF mRNA-positive cells in the crescents co-expressed the epithelial marker cytokeratin, but not a marker for macrophages. Moreover, TGF-beta1, its receptor TGF-beta receptor-I, and extracellular matrix molecules (collagen type I and fibronectin) were co-localized with CTGF mRNA-positive crescents. Our results suggest that CTGF is involved in extracellular matrix production in PECs and that it is one of the mediators promoting the scarring process in glomerular crescents.
Kanemoto
Katsuyoshi
K
Department of Pathology, Institute of Basic Medical Sciences, University of Tsukuba, Tennodai 1-1-1, 305-8575, Tsukuba, Ibaraki, Japan.
Usui
Joichi
J
Nitta
Kosaku
K
Horita
Shigeru
S
Harada
Atsumi
A
Koyama
Akio
A
Aten
Jan
J
Nagata
Michio
M
D030201:Activin Receptors, Type I / Q000032:analysis; D000328:Adult; D000368:Aged; D001706:Biopsy; D002675:Child, Preschool; D024042:Collagen Type I / Q000032:analysis; D055513:Connective Tissue Growth Factor; D004847:Epithelial Cells / Q000737:chemistry; D005260:Female; D005353:Fibronectins / Q000032:analysis; D015870:Gene Expression; D005921:Glomerulonephritis / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis / Q000235:genetics*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics*; D007633:Keratins / Q000032:analysis; D007668:Kidney / Q000737:chemistry; D007678:Kidney Glomerulus / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000032:analysis; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000032:analysis; D053773:Transforming Growth Factor beta1
C526317:CCN2 protein, human; D024042:Collagen Type I; D005353:Fibronectins; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; D007633:Keratins; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I