Effects of biomechanical forces on signaling in the cortical collecting duct (CCD)

Rolando Carrisoza-Gaytan, Yu Liu, Daniel Flores, Cindy Else, Heon Goo Lee, George Rhodes, Ruben M. Sandoval, Thomas R. Kleyman, Francis Young In Lee, Bruce Molitoris, Lisa M. Satlin, Rajeev Rohatgi

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

An increase in tubular fluid flow rate (TFF) stimulates Na reabsorption and K secretion in the cortical collecting duct (CCD) and subjects cells therein 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 affected by biomechanical forces. We hypothesized that FSS and CS differentially affect MAPK signaling and PGE2 release to modulate cation transport in the CCD. To validate that CS is a physiological force in vivo, we applied the intravital microscopic approach to rodent kidneys in vivo to show that saline or furosemide injection led to a 46.5 ± 2.0 or 170 ± 32% increase, respectively, in distal tubular diameter. Next, murine CCD (mpkCCD) cells were grown on glass or silicone coated with collagen type IV and subjected to 0 or 0.4 dyne/cm2 of FSS or 10% CS, respectively, forces chosen based on prior biomechanical modeling of ex vivo microperfused CCDs. Cells exposed to FSS expressed an approximately twofold greater abundance of phospho(p)-ERK and p-p38 vs. static cells, while CS did not alter p-p38 and p-ERK expression compared with unstretched controls. FSS induced whereas CS reduced PGE2 release by ~40%. In conclusion, FSS and CS differentially affect ERK and 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.

Original languageEnglish (US)
Pages (from-to)F195-F204
JournalAmerican Journal of Physiology - Renal Physiology
Volume307
Issue number2
DOIs
StatePublished - Jul 15 2014

Keywords

  • Collecting duct
  • Flow
  • Fluid shear stress
  • MAPK
  • Stretch

ASJC Scopus subject areas

  • Physiology
  • Urology

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    Carrisoza-Gaytan, R., Liu, Y., Flores, D., Else, C., Lee, H. G., Rhodes, G., Sandoval, R. M., Kleyman, T. R., Lee, F. Y. I., Molitoris, B., Satlin, L. M., & Rohatgi, R. (2014). Effects of biomechanical forces on signaling in the cortical collecting duct (CCD). American Journal of Physiology - Renal Physiology, 307(2), F195-F204. https://doi.org/10.1152/ajprenal.00634.2013