主催: 公益社団法人日本薬理学会
会議名: 第96回日本薬理学会年会
回次: 96
開催地: 横浜
開催日: 2022/11/30 - 2022/12/03
Transient Receptor Potential Canonical (TRPC) 6 is highly expressed in glomerular epithelial cells (podocytes) and is known to contribute to the maintenance of glomerular protein filtration. It has been reported that patients with nephrotic syndrome, which is a disease characterized by proteinuria due to renal glomerular damage, show elevated expression of TRPC6 that causes the disorganization of actin filaments in podocytes. It has also been reported that gain-of-function mutations of TRPC6 are associated with nephrotic syndrome. Therefore, specific inhibition of TRPC6 would be an attractive strategy for suppressing proteinuria.
In this study, we have identified a novel TRPC3/6 channels inhibitor, L862. To evaluate the effect of L862 on podocytes, MPC-5 (Mouse Podocyte Clone 5) were treated with L862. Comparison of the viability of L862-treated group to non-treated group showed no significant difference, indicating that L862 does not have toxicity at the cellular level. Next, we prepared MPC-5 cells treated with Puromycin Aminonucleoside (PAN), which is known to cause podocyte damage. Treatment of L862 to these damaged MPC-5 exhibited protective effect on cell morphology. These results suggest the potential of L862 as a drug for suppression of proteinuria.
