Integrin-dependent interactions with the extracellular matrix are important for tissue and organ development, including that of the kidney collecting duct (CD). Kidney CD cells co-express the main laminin-binding integrins α3β1, α6β1 and α6β4, but their relative contribution to CD development is not fully understood. Roy Zent and colleagues previously reported that deletion of the α3 or α6 integrin subunit in the ureteric bud (UB), which gives rise to the CD, results in only mild or no branching defects, respectively. In this study (Yazlovitskaya et al., 2021), the authors now assess whether α3 and α6 integrins cooperate in CD development by deleting both integrin subunits in the developing mouse UB. Surprisingly, the resulting double-knockout mice only had mild UB-branching defects at birth, but they all developed tubulointerstitial fibrosis and severe inflammation, and died of kidney failure by 14 months. Analysis of α3/α6-null CD cells showed that they acquire a leaky, more mesenchymal phenotype and produce excessive collagen and inflammatory cytokines, which is mediated by excessive activation of the NF-κB pathway. Taken together, these findings thus suggest that laminin-binding integrins are crucial for the maintenance of a tight CD epithelium by downregulating cytokine production though the NF-κB pathway, pointing to a previously unrecognised role of integrins in kidney cells.
