IDENTIFICATION, DISTRIBUTION, AND TISSULAR ORIGIN OF THE ALPHA-5(IV) AND ALPHA-6(IV) COLLAGEN CHAINS IN THE DEVELOPING HUMAN INTESTINE

The basement membrane type IV collagen is a family composed of six gen etically distinct but structurally similar polypeptide chains, alpha 1 -alpha 6. The alpha 1(IV) and alpha 2(IV) chains are ubiquitous compon ents of all BMs whereas the other four have a restricted tissue distri bution. In the present study, we have analyzed the expression, distrib ution, and cellular origin of the alpha 5(IV) and alpha 6(IV) chains i n the developing and adult human small intestine and in well-character ized in vitro models by indirect immunofluorescence, Western blot, and RT-PCR We have found that in the fetal small intestine, alpha 5(IV) a nd alpha 6(IV) are present in the epithelial BM and, in contrast to al pha 1(IV) and alpha 2(IV), are produced by both epithelial and mesench ymal cells. A distinct tissular origin for the alpha 1/alpha 2(IV) and alpha 5/alpha 6(IV) chains suggests that alpha 5(IV) and alpha 6(IV) associate as a heterotrimer in this organ We have also found that a pa rticular situation of alpha 5(IV)/alpha 6(IV) chain expression occurs in the adult intestine. Indeed, as compared with the fetal intestine, alpha 6(IV) chain production is maintained while the expression of the alpha 5(IV) chain is substantially reduced. Altered expression of the alpha 5(IV) chain was also observed in the differentiating enterocyti c-like Caco-2/15 cells, suggesting that in the intestinal model, the a lpha 5(IV) chain is subject to a regulated expression. Taken together, these observations indicate that the human intestinal epithelial BM c ontains up to four type IV collagen chains: the classical alpha 1(IV)/ alpha 2(IV) chains, which originate from mesenchymal cells, and the al pha 5(IV)/alpha 6(IV) chains, which are of both epithelial and mesench ymal origin and have their expression regulated throughout development . Dev. Dyn. 1998; 212:437-447. (C) 1998 Wiley-Liss, Inc.