PMID- 21109758
OWN - NLM
STAT- MEDLINE
DCOM- 20110722
LR  - 20211020
IS  - 1660-2137 (Electronic)
IS  - 1660-8151 (Print)
IS  - 1660-2137 (Linking)
VI  - 117
IP  - 4
DP  - 2011
TI  - Fluid shear stress induces renal epithelial gene expression through 
      polycystin-2-dependent trafficking of extracellular regulated kinase.
PG  - p27-36
LID - 10.1159/000321640 [doi]
AB  - BACKGROUND: The cilium and cilial proteins have emerged as principal 
      mechanosensors of renal epithelial cells responsible for translating mechanical 
      forces into intracellular signals. Polycystin-2 (PC-2), a cilial protein, 
      regulates flow/shear-induced changes in intracellular Ca(2+) ([Ca(2+)](i)) and 
      recently has been implicated in the regulation of mitogen-activated protein (MAP) 
      kinases. We hypothesize that fluid shear stress (FSS) activates PC-2 which 
      regulates MAP kinase and, in turn, induces MAP kinase-dependent gene expression, 
      specifically, monocyte chemoattractant protein-1 (MCP-1). METHODS: To test this, 
      PC-2 expression was constitutively reduced in a murine inner medullary collecting 
      duct (IMCD3) cell line, and the expression of FSS-induced MCP-1 expression and 
      MAP kinase signaling compared between the parental (PC-2-expressing) and 
      PC-2-deficient IMCD3 cells. RESULTS: FSS induces MAP kinase signaling and 
      downstream MCP-1 mRNA expression in wild-type IMCD3 cells, while inhibitors of 
      MAP kinase prevented the FSS-induced MCP-1 mRNA response. In contradistinction, 
      FSS did not induce MCP-1 mRNA expression in PC-2-deficient cells, but did 
      increase activation of the upstream MAP kinases. Wild-type cells exposed to FSS 
      augmented the nuclear abundance of activated MAP kinase while PC-2-deficient 
      cells did not. CONCLUSIONS: PC-2 regulates FSS-induced MAP kinase trafficking 
      into the nucleus of CD cells.
CI  - Copyright (c) 2010 S. Karger AG, Basel.
FAU - Flores, Daniel
AU  - Flores D
AD  - Department of Medicine, The Mount Sinai School of Medicine, New York, NY 
      10000209, USA.
FAU - Battini, Lorenzo
AU  - Battini L
FAU - Gusella, G Luca
AU  - Gusella GL
FAU - Rohatgi, Rajeev
AU  - Rohatgi R
LA  - eng
GR  - P30 DK074038/DK/NIDDK NIH HHS/United States
GR  - R01 DK078231/DK/NIDDK NIH HHS/United States
GR  - 5R24 CA095823-04/CA/NCI NIH HHS/United States
GR  - 1 S10 RR0 9145-01/RR/NCRR NIH HHS/United States
GR  - R24 CA095823/CA/NCI NIH HHS/United States
GR  - K08 DK062172/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20101123
PL  - Switzerland
TA  - Nephron Physiol
JT  - Nephron. Physiology
JID - 101159772
RN  - 0 (Anthracenes)
RN  - 0 (Butadienes)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Nitriles)
RN  - 0 (TRPP Cation Channels)
RN  - 0 (U 0126)
RN  - 0 (polycystic kidney disease 2 protein)
RN  - 1TW30Y2766 (pyrazolanthrone)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Anthracenes/pharmacology
MH  - Blotting, Western
MH  - Butadienes/pharmacology
MH  - Cell Line
MH  - Chemokine CCL2/genetics/metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Epithelial Cells/*metabolism
MH  - Extracellular Signal-Regulated MAP Kinases/antagonists & 
      inhibitors/genetics/metabolism
MH  - Fluorescent Antibody Technique
MH  - *Gene Expression Regulation
MH  - JNK Mitogen-Activated Protein Kinases/antagonists & 
      inhibitors/genetics/metabolism
MH  - Kidney Tubules, Collecting/cytology/metabolism
MH  - Mice
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors/*genetics/metabolism
MH  - Nitriles/pharmacology
MH  - RNA Interference
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Rheology
MH  - Stress, Mechanical
MH  - TRPP Cation Channels/*genetics/metabolism
PMC - PMC2997441
EDAT- 2010/11/27 06:00
MHDA- 2011/07/23 06:00
PMCR- 2012/04/01
CRDT- 2010/11/27 06:00
PHST- 2009/04/16 00:00 [received]
PHST- 2010/09/20 00:00 [accepted]
PHST- 2010/11/27 06:00 [entrez]
PHST- 2010/11/27 06:00 [pubmed]
PHST- 2011/07/23 06:00 [medline]
PHST- 2012/04/01 00:00 [pmc-release]
AID - 000321640 [pii]
AID - nep0117-0p27 [pii]
AID - 10.1159/000321640 [doi]
PST - ppublish
SO  - Nephron Physiol. 2011;117(4):p27-36. doi: 10.1159/000321640. Epub 2010 Nov 23.