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 24 h. However, in detail, this co-administration enhanced CTGF induction in PTEC during the first 8 h, and then decreased its expression, resulting in a rapid decrease in expression of the alpha1 (1) procollagen gene in TFB by 24 h. 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. (C) 2002 Elsevier Science (USA). All rights reserved.