FP078
Exosomal microRNAs derived from injured podocytes promote apoptosis of renal tubular cells through p38 activation

INTRODUCTION: Tubular injury and fibrosis are associated with a progressive decline of kidney function in advanced glomerular diseases. Podocytes are the key players in nearly all human glomerular diseases. Cross-talk between podocytes and tubular cells is believed to play an important role in the development of tubular injury. However, little is known about the exact pathological mechanisms involved in tubular injury. We hypothesized that the exosomal miRNAs derived from the injured podocytes lead to tubular epithelial cell damage.

METHODS: Tubular epithelial cells (HK-2 cells) were cultured with exosomes obtained from puromycin-treated human podocytes. The degree of HK-2 cells damage was assessed. We analyzed the microRNAs from puromycin-treated podocytes using next-generation sequencing (NGS). To validate the effects of exosomal microRNAs from injured podocytes on HK-2 cells, the tubular cells were treated with micro RNA mimics

RESULTS: Exosomes from injured podocytes induced apoptosis and p38 phosphorylation in the HK-2 cells. NGS generated reads for 154 microRNAs in the exosomes obtained from podocytes. Among these, we selected 5 microRNAs as candidates to induce tubular injury according to a literature-based search. These microRNA mimics also led to p38 phosphorylation and apoptosis of HK-2 cells.

CONCLUSIONS: MicroRNA-enriched exosomes from podocyte injury lead to apoptotic damage of tubular epithelial cells. These interactions may contribute to the development of tubular injury in glomerular diseases.