Laminin and Type IV Collagen Isoform Substitutions Occur in Temporally and Spatially Distinct Patterns in Developing Kidney Glomerular Basement Membranes

Kidney glomerular basement membranes (GBMs) undergo laminin and type IV collagen isoform substitutions during glomerular development, which are believed to be required for maturation of the filtration barrier. Specifically, GBMs of earliest glomeruli contain laminin 111 and collagen 121(IV), whereas mature glomeruli contain laminin 521 and collagen 345(IV). Here, we used confocal microscopy to simultaneously evaluate expression of different laminin and collagen IV isoforms in newborn mouse GBMs. Our results show loss of laminin 1 from GBMs in early capillary loop stages and continuous linear deposition of laminin bearing the 5 chain thereafter. In contrast, collagen 121(IV) persisted in linear patterns into late capillary loop stages, when collagen 345(IV) first appeared in discontinuous, non-linear patterns. This patchy pattern for collagen 345(IV) continued into maturing glomeruli where there were lengths of linear, laminin 5-positive GBM entirely lacking either isoform of collagen IV. Relative abundance of laminin and collagen IV mRNAs in newborn and 5-week-old mouse kidneys also differed, with those encoding laminin 1, 5, 1, 2, and 1, and collagen 1(IV) and 2(IV) chains all significantly declining at 5 weeks, but 3(IV) and 4(IV) were significantly upregulated. We conclude that different biosynthetic mechanisms control laminin and type IV collagen expression in developing glomeruli.