Fluid flow shear stress upregulates prostanoid receptor EP2 but not EP4 in murine podocytes

Podocytes in the glomerular filtration barrier regulate the passage of plasma proteins into urine. Capillary pressure and ultrafiltration impact the structure and function of podocytes. The mechanism of podocyte injury by fluid flow shear stress (FFSS) from hyperfiltration in chronic kidney disease (CKD) is not completely understood. Recently, we demonstrated increased synthesis of prostaglandin E2 in podocytes exposed to FFSS. Here, we determine the effect of FFSS on prostanoid receptors EP1–EP4 in cultured podocytes and in Os/+ mouse kidney, a model of hyperfiltration. Results of RT-PCR, qRT-PCR, immunoblotting and immunofluorescence studies indicate that cultured podocytes express EP1, EP2 and EP4 but not EP3. FFSS resulted in upregulated expression of only EP2 in podocytes. Kidney immunostaining showed significantly increased expression of EP2 in Os/+ mice compared with littermate controls. These novel results suggest that EP2 may be responsible for mediating podocyte injury from hyperfiltration-induced augmented FFSS in CKD.

► The mechanism of hyperfiltration-induced podocyte injury in CKD is not known.
► Podocytes are subjected to mechanical stretch and fluid flow shear stress (FFSS).
► PGE2 levels are increased in podocytes exposed to fluid flow shear stress in vitro.
► Cultured podocytes express EP1, EP2 and EP4 but not EP3.
► FFSS resulted in the upregulation of only EP2 in podocytes.