title: Effects of biomechanical forces on signaling in the cortical collecting duct (CCD).
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.
authors.affiliation: Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York;
authors.forename: Rolando
authors.initials: R
authors.lastname: Carrisoza-Gaytan
authors.affiliation: Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York;
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 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;
authors.forename: Daniel
authors.initials: D
authors.lastname: Flores
authors.affiliation: Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York;
authors.forename: Cindy
authors.initials: C
authors.lastname: Else
authors.affiliation: Department of Orthopedics, Robert Carroll and Jane Chace Carroll Laboratories, Columbia College of Physicians and Surgeons, New York, New York;
authors.forename: Heon Goo
authors.initials: HG
authors.lastname: Lee
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; and.
authors.forename: George
authors.initials: G
authors.lastname: Rhodes
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; and.
authors.forename: Ruben M
authors.initials: RM
authors.lastname: Sandoval
authors.affiliation: Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Kleyman
authors.affiliation: Department of Orthopedics, Robert Carroll and Jane Chace Carroll Laboratories, Columbia College of Physicians and Surgeons, New York, New York;
authors.forename: Francis Young-In
authors.initials: FY
authors.lastname: Lee
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; and.
authors.forename: Bruce
authors.initials: B
authors.lastname: Molitoris
authors.affiliation: 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;
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Satlin
authors.affiliation: 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.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Rohatgi
mesh_terms: D000818:Animals; D019898:Autocrine Communication; D002460:Cell Line; D015232:Dinoprostone / Q000378:metabolism; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005665:Furosemide / Q000008:administration & dosage; D007267:Injections; D017136:Ion Transport; D007672:Kidney Cortex / Q000187:drug effects / Q000502:physiology*; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000187:drug effects; D051379:Mice; D036641:Microscopy, Fluorescence, Multiphoton; D019899:Paracrine Communication; D010766:Phosphorylation; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000008:administration & dosage; D013314:Stress, Mechanical; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D012965:Sodium Chloride; D005665:Furosemide; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone; D011188:Potassium
keywords: MAPK; collecting duct; flow; fluid shear stress; prostaglandin E2; stretch