Format

Send to

Choose Destination
Am J Physiol Renal Physiol. 2014 Jul 15;307(2):F195-204. doi: 10.1152/ajprenal.00634.2013. Epub 2014 May 28.

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

Author information

1
Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York;
2
Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York;
3
Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Medicine, James J. Peters Veterans Affairs Medical Center, New York, New York;
4
Department of Orthopedics, Robert Carroll and Jane Chace Carroll Laboratories, Columbia College of Physicians and Surgeons, New York, New York;
5
Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; and.
6
Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
7
Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York;
8
Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Medicine, James J. Peters Veterans Affairs Medical Center, New York, New York; rajeev.rohatgi@mssm.edu.

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/cm(2) 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.

KEYWORDS:

MAPK; collecting duct; flow; fluid shear stress; prostaglandin E2; stretch

PMID:
24872319
PMCID:
PMC4152160
DOI:
10.1152/ajprenal.00634.2013
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center