Down‐regulation of α3(VI) chain expression by γ‐interferon decreases synthesis and deposition of collagen type VI

Abstract

Treatment of cultured human skin fibroblasts with increasing doses of γ-interferon produces a distinct reduction of steady-state levels of the α3 chain of collagen VI mRNA by about 60% but not of the α1 and α2 chain mRNAs. A similar decrease was also observed for collagen I and III mRNA while fibronectin mRNA remained at the same level. The decrease in α3(VI) mRNA is accompanied by a reduced synthesis of collagen VI and by a reduced deposition of both collagen VI and fibronectin in urea-insoluble form in the cell matrix. No other γ-interferon effects were observed for fibronectin biosynthesis. Immunoprecipitation of metabolically labeled collagen VI demonstrated a strongly reduced synthesis (by 65–80%) of intracellular α3(VI) chains with no decrease found for α1(VI) and α2(VI) chains. All three chains were, however, found to be reduced in the culture medium. Pepsin treatment of immunoprecipitated collagen VI showed similar chain ratios for material in the culture medium obtained in the absence or presence of γ-interferon. It indicates that correctly assembled heterotrimers of the composition [α1(VI) α2(VI) α3(VI)] are formed and secreted also in the absence of an equivalent α3(VI) chain synthesis but at a reduced rate. The data support previous predictions from sequence analyses [Chu et al. (1988) J. Biol. Chem. 263, 18601–18606] that collagen VI molecules composed of all three constituent chains are more stable than other assembly alternatives.