PRJNA526637
Depletion of GPRC5b prevent the inflammatory response on podocytes via NF-kB pathway regulation
Background Glomerulonephritis is a group of diseases that cause injuries in the renal glomerulus. Most of those diseases involve glomerular inflammation. NF-B is a pro-inflammatory transcription factor essential in the development of glomerulonephritis. In a previous work, we identified GPRC5b as a highly podocytes-enriched molecule. The role of GPRC5b in this cell type remains unclear, but GPRC5b has been related with the inflammatory response in other organs.Methods We generated a GPRC5b podocyte-specific knockout mouse line to determinate the role of GPRC5b in podocytes. In-vitro, we created a stable cells line of human podocytes over-expressing GPRC5b in order to understand the molecular mechanism behind GPRC5b.Results The deletion of GPRC5b in mouse podocytes did not have a significant impact in the development of the filtration barrier. Nevertheless, GPRC5b-cKO mice show a delay in the response to a single intraperitoneal injection of LPS. This delay was due to a lack of NF-B activation in KO mice. In-vitro, we show how GPRC5b over-expression in human podocytes generates a constitutive phosphorylation of P65.Conclusions GPRC5b has an important role in the regulation of NF-B pathway in mouse and human podocytes. We put forward GPRC5b as a new therapeutic target to prevent glomerular inflammation.