Background: Transient receptor potential Ankyrin 1 (TRPA1) is a non-selective cation channel primarily studied for its nociceptive role in neurons. However, more recent studies confirmed its expression in other tissues such as cardiac tissues where it facilitates ion transport. This study aimed (1) to evaluate the regulation of TRPA1; and (2) to determine the role of TRPA1 in the physiology of cardiac fibrosis in vitro.

Methods: Western blot was performed to check the TRPA1 protein levels in vitro (mouse cardiac fibroblasts) fibrotic model. RT-PCR analysis was used to measure gene expression while immunocytochemistry was used to visualize the protein expression in cells. To create an in vitro fibrotic model, mouse cardiac fibroblasts (MCF) were treated with rhTGFβ1 (5 ng/mL). On the other hand, to create a TRPA1 knockdown model, siRNA targeting TRPA1 was treated to the cells.

Results: TRPA1 levels in MCF were found to increase under fibrotic conditions. Meanwhile, knocking down TRPA1 using siRNA decreased the expression of fibrotic markers, α-SMA and col1a1. Accordingly, the decreased levels of TRPA1 under fibrotic conditions attenuated the phosphorylation of SMAD2 and ERK1/2 proteins which led to decreased fibrotic markers.

Conclusions: The findings of this study showed that inhibition of TRPA1 is a potential strategy in addressing against TGF-β1-induced cardiac fibrosis. The study also provided evidence that TRPA1 affects the progression of fibrosis through the fibrotic ERK1/2 signaling pathway.