Cutis Laxa Skin Fibroblast Strain

Skin fibroblasts from two cases of autosomal recessive cutis laxa (CL), having insignificant elastin production and mRNA levels, were challenged with transforming growth factor beta-i (TGF-fi1). Elastin production was brought from undetectable values to amounts typical of normal human skin fibroblasts in a dose-dependent fashion. Basic fibroblast growth factor (100 ng/ml) alone or in combination with TGF-,B1 reduced elastin production and mRNA expression in CL skin fibroblasts more extensively than in normal cells. In situ hybridization showed that these effects were at the transcript level. One of the CL strains was examined in detail. Transcription rates for elastin were similar in normal and CL and unchanged by TGF-,fl or TGF-P2 (10 ng/ml), while in CL elastin mRNA half-life was increased > 10-fold by TGF-p2 and reduced 6-fold after TGF-,82 withdrawal, as compared with a control strain. Cycloheximide partially reversed elastin mRNA instability. These data are consistent with a defect in elastin mRNA stability that requires synthesis of labile factors or intact translational machinery, resulting in an extremely low steady state level ofmRNA present in this strain of CL. Furthermore, TGF-j3 can relieve elastin mRNA instability in at least one CL strain and elastin production defects in both CL strains. (J. Clin. Invest. 1995. 95:986-994.)