Kindlins are a family of three integrin-binding proteins that transduce biochemical signals involved in cell migration, proliferation, and the formation and function of tissues.
Mutations in and overproduction of kindlins have been associated with a wide range of human diseases including atherosclerosis and heart failure, polycystic ovary syndrome and glomerular disease, neuropathic pain, immune deficiency, and kidney fibrosis.
But kindlins do more than transduce signals through transmembrane integrin receptors.
Using mouse models and cell culture experiments, researchers at Vanderbilt Health demonstrated that these proteins regulate both cellular and extracellular matrix interactions and growth factor signaling during the formation of ureteric buds, a key step in the development of the kidneys’ urine collection system.
Their findings, reported Feb. 9 in the journal Development, “improve our understanding of the mechanisms of kidney development and expand our knowledge of integrin functions,” said the paper’s corresponding author, Roy Zent, MD, the Thomas F. Frist Sr. Professor of Medicine.
The paper’s co-first authors were Shensen Li, MD, PhD, a postdoctoral research fellow in the Zent lab, and Fabian Bock, MD, PhD, assistant professor of Medicine, both in the Division of Nephrology and Hypertension.
Other co-authors currently at Vanderbilt were Olga Viquez, PhD, Anjana Hassan, MD, MBA, Glenda Mernaugh, Xinyu Dong, Meiling Melzer, Matthew Tantengco, Andrew Terker, MD, PhD, Juan Pablo Arroyo, MD, PhD, and Ambra Pozzi, PhD.
The research was supported in part by National Institutes of Health grants K08DK134879, R01DK069921, R01DK088327, R01DK127589, and R01DK119212, and by the Department of Veterans Affairs, the Southern Society for Clinical Investigation, Kidney Cure and the W. M. Keck Foundation.
