Biomechanical forces differentially regulate signaling in the cortical collecting duct (CCD)

Abstract

Tubular fluid flow (TFF) stimulates Na reabsorption and K secretion in the CCD and subjects CCD cells to biomechanical forces including fluid shear stress (FSS) and circumferential stretch (CS). Intracellular MAPK and extracellular autocrine/paracrine PGE2 signaling regulate cation transport in the CCD and, at least in other systems, are regulated by biomechanical forces. We hypothesized that FSS and CS differentially regulate MAPK signaling and PGE2 release to modulate cation transport in the CCD. Murine CCD cells (mpkCCD) were grown on glass or silicone coated with collagen I, and subjected to 0 or 0.4 dynes/cm2 of FSS or 10% CS. Cells exposed to FSS (3–60 min; n=4–9) expressed greater abundance of phospho(p)‐ERK and p‐p38 than static cells (n=4–9), while CS suppressed p‐p38 expression (n=5) compared to nonstretched cells (n=5). p‐ERK abundance was unaffected by CS. FSS induced PGE2 release; however, CS reduced PGE2 release (0.35±0.07 pg/mL/ug protein [n=8] vs. 0.15±0.02 pg/mL/ug protein [n=9]) into the media bathing mpkCCD cells. In conclusion, FSS and CS differentially regulate p38 activation and PGE2 release in a cell culture model of the CD. We speculate that TFF differentially regulates biomechanical signaling and, in turn, cation transport in the CCD.