PS-BPB06-2: PIEZO2 EXPRESSION AND ITS ALTERATION BY MECHANICAL FORCES IN MOUSE MESANGIAL CELLS AND RENIN PRODUCING CELLS

Abstract

The kidney plays a central role in body fluid homeostasis. Cells in the glomeruli and juxtaglomerular apparatus sense mechanical forces and modulate glomerular filtration and renin release. However, details of mechanosensory systems in these cells are unclear. Piezo2 is a recently identified mechanically activated ion channel found in various tissues, especially sensory neurons. Herein, we examined Piezo2 expression and regulation in mouse kidneys. RNAscope in situ hybridization revealed that Piezo2 expression was highly localized in mesangial cells and juxtaglomerular renin producing cells. Immunofluorescence assays detected GFP signals in mesangial cells and juxtaglomerular renin producing cells of Piezo2GFP reporter mice. Piezo2 transcripts were observed in the Foxd1 positive stromal progenitor cells of the metanephric mesenchyme in the developing mouse kidney, which are precursors of mesangial cells and renin producing cells. In a mouse model of dehydration, Piezo2 expression was downregulated in mesangial cells and upregulated in juxtaglomerular renin producing cells, along with the overproduction of renin and enlargement of the area of renin producing cells. Furthermore, the expression of the renin coding gene Ren1 was reduced by Piezo2 knockdown in cultured juxtaglomerular As4.1 cells under static and stretched conditions. These data suggest pivotal roles for Piezo2 in the regulation of glomerular filtration and body fluid balance.