The kidney is responsible for retaining essential proteins and removing waste products from the blood stream. The kidney filter is maintained by an intricate structure formed by the actin-rich foot process of podocytes that surround the glomerular capillaries. Injury to the kidney promotes a signaling cascade that results in cytoskeletal remodeling, effacement of podocyte foot processes, and loss of the filter function, which can ultimately result in kidney failure. Thomas Schaldecker, Sookyung Kim, Constantine Tarabanis and colleagues at Massachusetts General Hospital discovered that mice lacking the ion channel TRPC5 were protected from podocyte effacement and loss of the kidney filtration barrier following kidney injury. Using live imaging, the authors found that in the absence of TRPC5, podocytes were protected from cytoskeletal remodeling in response to injury, thereby keeping the filter in tact. Furthermore, the authors demonstrated that pharmacological inhibition of TRPC5 protects animals from protein loss in the urine following kidney injury. This study indicates that activation of ion channel TRPC5 following kidney injury promotes loss of kidney filter function, and inhibition of this ion channel may have therapeutic potential. The accompanying indexed color image of a podocyte reveals intricate cytoskeletal structures using Life-Act technology. This image highlights the importance of the podocyte actin cytoskeleton to maintain an intact kidney filter barrier.
An intact kidney filter is vital to retention of essential proteins in the blood and removal of waste from the body. Damage to the filtration barrier results in albumin loss in the urine, a hallmark of cardiovascular disease and kidney failure. Here we found that the ion channel TRPC5 mediates filtration barrier injury. Using
Thomas Schaldecker, Sookyung Kim, Constantine Tarabanis, Dequan Tian, Samy Hakroush, Philip Castonguay, Wooin Ahn, Hanna Wallentin, Hans Heid, Corey R. Hopkins, Craig W. Lindsley, Antonio Riccio, Lisa Buvall, Astrid Weins, Anna Greka