TGF-beta1 and HGF coordinately facilitate collagen turnover in subepithelial mesenchyme.
We have employed co-culture of proximal tubular epithelial cells (PTEC) and renal tubulo-interstitial fibroblasts (TFB) to study the role of transforming growth factor-beta1 (TGF-beta1) and hepatocyte growth factor (HGF) in epithelial-mesenchymal interactions. In co-culture, TGF-beta1 stimulated TFB to produce type I collagen (COLI). This effect was both direct and indirect, via connective tissue growth factor (CTGF) produced by the co-cultured PTEC. Co-administration of TGF-beta1 and HGF significantly increased overall COLI production by TFB by 24h. However, in detail, this co-administration enhanced CTGF induction in PTEC during the first 8h, and then decreased its expression, resulting in a rapid decrease in expression of the alpha1(I) procollagen gene in TFB by 24h. Additionally, tissue inhibitor of metalloproteinase-1 was induced in PTEC by TGF-beta1 with or without co-administration of HGF, which contributed to the COLI accumulation. In contrast, HGF alone or co-administered with TGF-beta1 significantly increased collagenolytic activity derived from PTEC. Therefore, TGF-beta1 and HGF seem to coordinately modulate epithelial-mesenchymal interactions to facilitate COLI turnover in subepithelial mesenchyme.
Inoue
Tsutomu
T
Department of Nephrology, Saitama Medical College, 38 Morohongo, Moroyama-machi, Irumagun, Japan.
Okada
Hirokazu
H
Kobayashi
Tatsuya
T
Watanabe
Yusuke
Y
Kikuta
Tomohiro
T
Kanno
Yoshihiko
Y
Takigawa
Masaharu
M
Suzuki
Hiromichi
H
D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D024042:Collagen Type I / Q000378:metabolism*; D055513:Connective Tissue Growth Factor; D004848:Epithelium / Q000187:drug effects* / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007684:Kidney Tubules / Q000033:anatomy & histology / Q000187:drug effects; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
C526317:CCN2 protein, human; C526318:CCN2 protein, mouse; D024042:Collagen Type I; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; D017228:Hepatocyte Growth Factor