# EIF4A3-induced circFAT1 promotes high glucose-induced podocyte damage via miR-30e-5p/SOX4 axis

## TL;DR

This study shows that circFAT1, a circular RNA, contributes to kidney damage in diabetic nephropathy by promoting podocyte injury through a specific molecular pathway.

## Contribution

The study identifies a novel regulatory mechanism involving circFAT1, miR-30e-5p, and SOX4 in high glucose-induced podocyte damage.

## Key findings

- circFAT1 is upregulated in podocytes under high glucose conditions and promotes epithelial-mesenchymal transition.
- Inhibition of circFAT1 reduces podocyte migration and restores differentiation markers.
- Elevated circFAT1 levels correlate with disease severity in diabetic nephropathy patients.

## Abstract

Podocyte injury significantly contributes to glomerular filtration dysfunction and albuminuria in diabetic nephropathy (DN). Circular RNAs, particularly circFAT1 (hsa_circ_0001461), have emerged as influential regulators in pathological processes. This research focused on exploring the function of hsa_circ_0001461 in high glucose (HG)-induced podocyte damage and the associated underlying mechanism. Here, we demonstrate that circFAT1 is significantly upregulated in HPCs under HG conditions. Inhibition of circFAT1 led to decreased podocyte migration and a restoration of differentiation markers, along with a reduction in mesenchymal markers. Mechanistically, circFAT1 was found to inhibit miR-30e-5p, resulting in enhanced SOX4 expression, which promoted epithelial-mesenchymal transition and migration in podocytes. Moreover, we identified EIF4A3 as a crucial regulator of circFAT1 biogenesis under hyperglycaemic conditions. Importantly, elevated levels of circFAT1 were also detected in DN patients, correlating with increased albuminuria and serum creatinine. In conclusion, this study elucidates the critical role of circFAT1 in HG-induced podocyte injury through the miR-30e-5p/SOX4 signalling pathway. The findings suggest that targeting circFAT1 May offer a potential strategy for DN intervention.