Transmembrane receptors called integrins and proteins called laminins play important roles in the formation and function of tissues, including the ducts that collect urine from the filtering units of the kidneys.
To better understand their role, Roy Zent, MBBCh, PhD, and colleagues deleted the alpha-3 and alpha-6 subunits of laminin-binding integrins in the developing kidney collecting system of the mouse.
Surprisingly, the deletions had little effect on kidney collecting system development. However, the mice developed severe inflammation around the collecting ducts and fibrosis (scarring) that was fatal within 14 months.
The inflammation resulted from activation of the nuclear factor-kappa B (NF-kappaB) pro-inflammatory signaling pathway, and loss of polarity, or proper orientation of the epithelial cells lining the ducts, which allowed the invasion of inflammatory cells.
These results, reported Nov. 29 in the Journal of Cell Science, suggest that laminin-binding integrins play a critical role in maintaining polarity of kidney tubule epithelial cells and downregulating inflammatory cytokine secretion by modulating the NF-kappaB signaling pathway.
The research was supported by the U.S. Department of Veterans Affairs, National Institutes of Health grants DK069921, HL151016, HL127102, HL154287 and DK119212, the Vanderbilt O’Brien Kidney Center and an American Society of Nephrology Ben J. Lipps Research Fellowship.
