Project Grant R03DK149304

Summary

Boston Children's Hospital received a $133,500 Project Grant from the National Institute of Diabetes and Digestive and Kidney Diseases under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847), awarded July 6, 2026, with completion targeted for April 30, 2028. The two-year research project investigates integrin αVβ6-mediated activation of latent transforming growth factor beta 2 (TGF-β2) as a driver of renal fibrosis and explores this pathway as a potential therapeutic target. The research addresses the critical clinical problem of progression from acute kidney injury to chronic kidney disease and end-stage renal disease.

The grant funds two primary research aims: (1) mapping the spatial distribution and cellular interactions of pro-TGF-β2 and integrin αVβ6 in the renal fibrotic niche using advanced imaging techniques including confocal microscopy, STED super-resolution microscopy, and proximity ligation assays to define the cell types comprising the pro-TGF-β2 expression and activation network during kidney injury; and (2) testing whether abolishing αVβ6-mediated TGF-β2 activation in genetically modified mice attenuates renal fibrosis progression. The research leverages preliminary data demonstrating increased pro-TGF-β2 expression and macrophage recruitment in the interstitium following kidney injury, with potential implications for developing novel fibrosis-suppressing therapeutics.