Science Paper Examines Molecular Contributors to Kidney Fibrosis

A genetic study of mice and humans in this week's Science Signaling has identified new molecular contributors to kidney fibrosis. Chronic kidney disease and kidney injury often result in renal fibrosis, but the mechanisms underlying fibrogenesis are not entirely clear. In the study, a University of Manchester-led team used RNA sequencing and other techniques to study kidney fibrosis in human patients and in mice with experimentally induced kidney injury. They found that the transcription factor SOX9 is involved in fibrosis in both the humans and the animals, with Neuron navigator 3 (NAV3) acting downstream of SOX9. In mice, knocking out Sox9 reduced injury-induced kidney fibrosis and an associated increase in Nav3 expression, while experiments in an in vitro model of renal pericyte transdifferentiation into myofibroblasts showed that NAV3 is required for multiple aspects of fibrogenesis. "Our work identifies a SOX9-NAV3-YAP1 axis involved in the progression of kidney fibrosis and points to NAV3 as a potential target for pharmacological intervention," the study's authors write.