Regulation of heat shock protein 47 and type I procollagen expression in avian tendon cells.

Heat shock protein 47 (Hsp47) is a collagen-binding stress protein that acts as a collagen-specific molecular chaperone during the biosynthesis and secretion of procollagen. Type I collagen is a major component of tendons. Coexpression of genes for both proteins has been reported in various tissues, where many growth factors likely regulate their expressions in different ways. Here we describe the effects of increased temperature, mechanical stress and growth factors on Hsp47 and type I procollagen expression in embryonic chicken tendon cells. The expression of Hsp47 mRNA at 45 degrees C increased within 60 min and returned to baseline in 4 h after the temperature decreased to 37 degrees C. Our data also show that transforming growth factor beta1 (TGF-beta1) is another regulator of Hsp47 expression as the addition of TGF-beta1 led to a moderate increase in the expression of Hsp47 mRNA. TGF-beta2 and TGF-beta3 exerted only a small effect; epidermal growth factor and tumor necrosis factor alpha (TNF-alpha) had none. TGF-beta1 increased type I procollagen mRNA expression and TNF-alpha reduced this expression. TGF-beta1 delayed the degradation of Hsp47 mRNA after heat shock likely via post-transcriptional regulation of the Hsp47 gene. We also report that mechanical stress increased Hsp47 mRNA expression and Hsp47 protein synthesis. Induction of Hsp47 protein expression by heat shock, mechanical stress and TGF-beta1 was likely achieved through activation and translocation of heat shock transcription factor 1 into the nucleus. Our data indicate that TGF-beta1 is a major regulator of both procollagen and Hsp47 genes.