Identification, distribution, and tissular origin of the α5(IV) and α6(IV) collagen chains in the developing human intestine

The basement membrane type IV collagen is a family composed of six genetically distinct but structurally similar polypeptide chains, α1–α6. The α1(IV) and α2(IV) chains are ubiquitous components of all BMs whereas the other four have a restricted tissue distribution. In the present study, we have analyzed the expression, distribution, and cellular origin of the α5(IV) and α6(IV) chains in the developing and adult human small intestine and in well-characterized in vitro models by indirect immunofluorescence, Western blot, and RT-PCR. We have found that in the fetal small intestine, α5(IV) and α6(IV) are present in the epithelial BM and, in contrast to α1(IV) and α2(IV), are produced by both epithelial and mesenchymal cells. A distinct tissular origin for the α1/α2(IV) and α5/α6(IV) chains suggests that α5(IV) and α6(IV) associate as a heterotrimer in this organ. We have also found that a particular situation of α5(IV)/α6(IV) chain expression occurs in the adult intestine. Indeed, as compared with the fetal intestine, α6(IV) chain production is maintained while the expression of the α5(IV) chain is substantially reduced. Altered expression of the α5(IV) chain was also observed in the differentiating enterocytic-like Caco-2/15 cells, suggesting that in the intestinal model, the α5(IV) chain is subject to a regulated expression. Taken together, these observations indicate that the human intestinal epithelial BM contains up to four type IV collagen chains: the classical α1(IV)/α2(IV) chains, which originate from mesenchymal cells, and the α5(IV)/α6(IV) chains, which are of both epithelial and mesenchymal origin and have their expression regulated throughout development. Dev. Dyn. 1998; 212:437–447.