CORTICOSTEROIDS INCREASE PROCOLLAGEN GENE-EXPRESSION, SYNTHESIS, AND SECRETION BY HUMAN INTESTINAL SMOOTH-MUSCLE CELLS

Background & Aims: Collagen synthesis by smooth muscle cells plays an important role in intestinal fibrosis, Corticosteroids inhibit collagen synthesis in fibroblasts. The aim of this study was to examine the effect of corticosteroids on the expression of collagen by human intestinal smooth muscle (HISM) cells in vitro. Methods: Collagen synthesis was determined by the sensitivity of radiolabeled protein to collagenase, Secretion was determined by polyacrylamide gel electrophoresis of radiolabeled procollagen in the medium. Procollagen messenger RNA was determined by Northern blot analysis. Results: Collagen synthesis by confluent HISM cells was not affected by corticosteroids at 10(-10) to 10(-5) mol/L but, in subconfluent cultures, was nonspecifically increased 50% at 10(-5) mol/L, Procollagen secretion was nonspecifically increased 60% at 10(-6) mol/L dexamethasone without any effect on the type III/I ratio, Procollagen I and III messenger RNA levels responded in a biphasic manner: a 45%-65% increase at 10(-10) mol/L and a 15% and 30% decrease at 10(-8) and 10(-6) mol/L, In fibroblasts, collagen synthesis was inhibited 85% by dexamethasone, procollagen secretion was decreased 70%, the type III/I ratio decreased from 70:1 to 18:1, and procollagen messenger RNA was inhibited 25% and 60% (types I and III). Conclusions: Collagen expression by HISM cells is refractory to corticosteroids and, at certain concentrations, is augmented.