THE ALPHA-1-ALPHA-6 SUBUNITS OF INTEGRINS ARE CHARACTERISTICALLY EXPRESSED IN DISTINCT SEGMENTS OF DEVELOPING AND ADULT HUMAN NEPHRON

We studied the distribution of the α1-α6 subunits of β1 integrins in developing and adult human kidney using a panel of mAbs in indirect immunofluorescence microscopy. Uninduced mesenchyme displayed a diffuse immunoreactivity for only the α1 integrin subunit. At the S-shaped body stage of nephron development, several of the α subunits were characteristically expressed in distinct fetal nephron segments, and the pattern was retained also in the adult nephron. Thus, the α1 subunit was characteristically expressed in mesangial and endothelial cells, the α2 in glomerular endothelium and distal tubules, the α3 in podocytes, Bowman's capsule, and distal tubules, and the α6 subunit basally in all tubules, and only transiently in podocytes during development. Unlike the α3 and α6 subunits, the α2 subunit displayed an overall cell surface distribution in distal tubules. It was also distinctly expressed in glomerular endothelia during glomerulo-genesis. The β4 subunit was expressed only in fetal collecting ducts, and hence the α6 subunit seems to be complexed with the β1 rather than β4 subunit in human kidney. Of the two fibronectin receptor α subunits, α4 and α5, only the latter was expressed, confined to endothelia of developing and adult blood vessels, suggesting that these receptor complexes play a minor role during nephrogenesis. The present results suggest that distinct integrins play a role during differentiation of specific nephron segments. They also indicate that α3β1 and α6β1 integrin complexes may function as basement membrane receptors in podocytes and tubular epithelial cells.