PMID- 24905090
OWN - NLM
STAT- MEDLINE
DCOM- 20150130
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 6
DP  - 2014
TI  - Calcium sensing receptor modulates extracellular calcium entry and proliferation 
      via TRPC3/6 channels in cultured human mesangial cells.
PG  - e98777
LID - 10.1371/journal.pone.0098777 [doi]
LID - e98777
AB  - Calcium-sensing receptor (CaSR) has been demonstrated to be present in several 
      tissues and cells unrelated to systemic calcium homeostasis, where it regulates a 
      series of diverse cellular functions. A previous study indicated that CaSR is 
      expressed in mouse glomerular mesangial cells (MCs), and stimulation of CaSR 
      induces cell proliferation. However, the signaling cascades initiated by CaSR 
      activation in MCs are currently unknown. In this study, our data demonstrate that 
      CaSR mRNA and protein are expressed in a human mesangial cell line. Activating 
      CaSR with high extracellular Ca2+ concentration ([Ca2+]o) or spermine induces a 
      phospholipase C (PLC)-dependent increase in intracellular Ca2+ concentration 
      ([Ca2+]i). Interestingly, the CaSR activation-induced increase in [Ca2+]i results 
      not only from intracellular Ca2+ release from internal stores but also from 
      canonical transient receptor potential (TRPC)-dependent Ca2+ influx. This 
      increase in Ca2+ was attenuated by treatment with a nonselective TRPC channel 
      blocker but not by treatment with a voltage-gated calcium blocker or Na+/Ca2+ 
      exchanger inhibitor. Furthermore, stimulation of CaSR by high [Ca2+]o enhanced 
      the expression of TRPC3 and TRPC6 but not TRPC1 and TRPC4, and siRNA targeting 
      TRPC3 and TRPC6 attenuated the CaSR activation-induced [Ca2+]i increase. Further 
      experiments indicate that 1-oleoyl-2-acetyl-sn-glycerol (OAG), a known activator 
      of receptor-operated calcium channels, significantly enhances the CaSR 
      activation-induced [Ca2+]i increase. Moreover, under conditions in which 
      intracellular stores were already depleted with thapsigargin (TG), CaSR agonists 
      also induced an increase in [Ca2+]i, suggesting that calcium influx stimulated by 
      CaSR agonists does not require the release of calcium stores. Finally, our data 
      indicate that pharmacological inhibition and knock down of TRPC3 and TRPC6 
      attenuates the CaSR activation-induced cell proliferation in human MCs. With 
      these data, we conclude that CaSR activation mediates Ca2+ influx and cell 
      proliferation via TRPC3 and TRPC6 in human MCs.
FAU - Meng, Kexin
AU  - Meng K
AD  - Department of Nephrology, The Second Affiliated Hospital, Harbin Medical 
      University, Harbin, China.
FAU - Xu, Jia
AU  - Xu J
AD  - Department of Nephrology, The Fourth Affiliated Hospital, Harbin Medical 
      University, Harbin, China.
FAU - Zhang, Chengwei
AU  - Zhang C
AD  - Department of Nephrology, The Second Affiliated Hospital, Harbin Medical 
      University, Harbin, China.
FAU - Zhang, Rui
AU  - Zhang R
AD  - Department of Nephrology, The Second Affiliated Hospital, Harbin Medical 
      University, Harbin, China.
FAU - Yang, He
AU  - Yang H
AD  - Department of Nephrology, The Second Affiliated Hospital, Harbin Medical 
      University, Harbin, China.
FAU - Liao, Chang
AU  - Liao C
AD  - Department of Nephrology, The Second Affiliated Hospital, Harbin Medical 
      University, Harbin, China.
FAU - Jiao, Jundong
AU  - Jiao J
AD  - Department of Nephrology, The Second Affiliated Hospital, Harbin Medical 
      University, Harbin, China; Institute of Nephrology, Harbin Medical University, 
      Harbin, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140606
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Receptors, Calcium-Sensing)
RN  - 0 (TRPC Cation Channels)
RN  - 0 (TRPC3 cation channel)
RN  - 0 (TRPC6 Cation Channel)
RN  - 0 (TRPC6 protein, human)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Biological Transport/drug effects
MH  - Calcium/*metabolism
MH  - Cell Line
MH  - Cell Proliferation/drug effects
MH  - Extracellular Space/drug effects/*metabolism
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Mesangial Cells/*cytology/*metabolism
MH  - Mice
MH  - Receptors, Calcium-Sensing/agonists/*metabolism
MH  - TRPC Cation Channels/antagonists & inhibitors/genetics/*metabolism
MH  - TRPC6 Cation Channel
PMC - PMC4048219
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/06/07 06:00
MHDA- 2015/01/31 06:00
PMCR- 2014/06/06
CRDT- 2014/06/07 06:00
PHST- 2014/02/13 00:00 [received]
PHST- 2014/05/07 00:00 [accepted]
PHST- 2014/06/07 06:00 [entrez]
PHST- 2014/06/07 06:00 [pubmed]
PHST- 2015/01/31 06:00 [medline]
PHST- 2014/06/06 00:00 [pmc-release]
AID - PONE-D-14-06899 [pii]
AID - 10.1371/journal.pone.0098777 [doi]
PST - epublish
SO  - PLoS One. 2014 Jun 6;9(6):e98777. doi: 10.1371/journal.pone.0098777. eCollection 
      2014.