scRNA-Seq reveals anti-fibrotic mechanisms of TRPC6 inhibition [Spatial Transcriptomics]

Inhibition of transient receptor potential canonical 6 channels (TRPC6) alleviates tubular injury and renal fibrosis induced by unilateral ureteral obstruction (UUO).However, the exact renoprotective mechanisms are unknown. In this study, we utilized single-cell RNA sequencing (scRNA-Seq) to define the cellular and transcriptional landscape associated with renoprotection through in vivo TRPC6 inhibition, specifically using SH045 (larixyl N-methylcarbamate), in the UUO model. Six C57BL/6 mice underwent unilateral ureteral obstruction (UUO) surgery. Seven days post-surgery, the kidneys from Vehicle-treated (n=3) and SH045-treated (n=3) mice were harvested. The contralateral kidneys from Vehicle-treated mice (n=3) served as the control group (Ctrl group). A total of nine kidney samples were used for single-cell RNA sequencing (scRNA-seq). Additionally, two of these samples (one from the SH045 group and one from the Vehicle group) were simultaneously analyzed using spatial transcriptomics.