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Regulation of TRPC6 Channels by Non-Steroidal Anti-Inflammatory Drugs
D V Ilatovskaya1,2, T S Pavlov1, Y A Negulyaev2
1Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA.
Non-steroidal anti-inflammatory drugs (NSAID) like diclofenac may treat focal segmental glomerulosclerosis (FSGS) by targeting TRPC6 channels in kidney podocytes, offering a potential therapeutic avenue for this nephrotic syndrome.
Area of Science:
- Nephrology
- Molecular Biology
- Pharmacology
Background:
- Family focal segmental glomerulosclerosis (FSGS) is a kidney disorder causing nephrotic syndrome, often linked to TRPC6 channel mutations.
- TRPC6 channels are expressed in podocytes, the kidney cells affected in FSGS.
- Previous studies indicated NSAIDs inhibit TRPC-like channels in rat glomeruli.
Purpose of the Study:
- To investigate the effect of diclofenac on wild-type and mutated TRPC6 channels.
- To explore TRPC6 channels as a potential therapeutic target for FSGS.
Main Methods:
- Functional reconstitution of TRPC6 channels in HEK 293 and CHO cell lines.
- Intracellular calcium level measurements.
- Patch-clamp electrophysiology to assess channel activity.
Main Results:
- TRPC6 P112Q mutant channels showed increased activity compared to wild-type channels.
- Diclofenac inhibited single TRPC6 channel activity.
- Diclofenac reduced whole-cell current in cells overexpressing TRPC6 P112Q.
Conclusions:
- TRPC6 channels, particularly the P112Q variant, are functionally modulated by diclofenac.
- TRPC6 channels represent a potential therapeutic target for NSAID intervention in FSGS treatment.
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