Attenuated mesangial cell proliferation related to store-operated Ca 2+ entry in aged rat: The role of STIM 1 and Orai 1

Bing Shen; Jinhang Zhu; Jin Zhang; Feifei Jiang; Zhaoyi Wang; Yang Zhang; Jie Li; Dake Huang; Daoping Ke; Rong Ma; Juan Du

doi:10.1007/s11357-013-9511-5

Attenuated mesangial cell proliferation related to store-operated Ca ²⁺ entry in aged rat: The role of STIM 1 and Orai 1

Bing Shen, Jinhang Zhu, Jin Zhang, Feifei Jiang, Zhaoyi Wang, Yang Zhang, Jie Li, Dake Huang, Daoping Ke, Rong Ma, Juan Du

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16 Scopus citations

Abstract

Store-operated Ca²⁺ entry (SOCE) is a common and ubiquitous mechanism regulating Ca²⁺ influx into cells and participates in numerous biological processes including cell proliferation. Glomerular mesangial cells (GMCs) play a role in the regulation of the glomerular filtration rate. From a clinical point of view, many physiological functions alter with age. In the present study, we used angiotensin II, glucagonand the sarco/endoplasmic reticulum membrane Ca²⁺ pump inhibitor thapsigargin to deplete the internal Ca²⁺ stores for the activation of SOCE. We found that SOCE was significantly attenuated in GMCs from aged (22-month-old) rats. The expression of SOCErelated components, stromal interaction molecule 1 (STIM 1) and Orai 1, in freshly isolated glomeruli notably decreased, and STIM 1 and Orai 1 puncta formation significantly reduced in primary-cultured GMCs in aged rats. Moreover, specific knockdown of STIM 1 and Orai 1 by small interfering RNA markedly suppressed SOCE and cell proliferation of GMCs isolated from young (3-month-old) rats. We conclude that the attenuation of GMCs proliferation can be attributed to the decreased SOCE partially caused by reduced expression of STIM 1 and Orai 1.

Original language	English
Pages (from-to)	2193-2202
Number of pages	10
Journal	Age
Volume	35
Issue number	6
DOIs	https://doi.org/10.1007/s11357-013-9511-5
State	Published - Dec 2013

Keywords

Aging
Glomerular mesangial cell
Orai 1
Proliferation
STIM 1

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10.1007/s11357-013-9511-5

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@article{127484b3ff0849a88049436f3aee006f,

title = "Attenuated mesangial cell proliferation related to store-operated Ca 2+ entry in aged rat: The role of STIM 1 and Orai 1",

abstract = "Store-operated Ca2+ entry (SOCE) is a common and ubiquitous mechanism regulating Ca2+ influx into cells and participates in numerous biological processes including cell proliferation. Glomerular mesangial cells (GMCs) play a role in the regulation of the glomerular filtration rate. From a clinical point of view, many physiological functions alter with age. In the present study, we used angiotensin II, glucagonand the sarco/endoplasmic reticulum membrane Ca2+ pump inhibitor thapsigargin to deplete the internal Ca2+ stores for the activation of SOCE. We found that SOCE was significantly attenuated in GMCs from aged (22-month-old) rats. The expression of SOCErelated components, stromal interaction molecule 1 (STIM 1) and Orai 1, in freshly isolated glomeruli notably decreased, and STIM 1 and Orai 1 puncta formation significantly reduced in primary-cultured GMCs in aged rats. Moreover, specific knockdown of STIM 1 and Orai 1 by small interfering RNA markedly suppressed SOCE and cell proliferation of GMCs isolated from young (3-month-old) rats. We conclude that the attenuation of GMCs proliferation can be attributed to the decreased SOCE partially caused by reduced expression of STIM 1 and Orai 1.",

keywords = "Aging, Glomerular mesangial cell, Orai 1, Proliferation, STIM 1",

author = "Bing Shen and Jinhang Zhu and Jin Zhang and Feifei Jiang and Zhaoyi Wang and Yang Zhang and Jie Li and Dake Huang and Daoping Ke and Rong Ma and Juan Du",

note = "Funding Information: Acknowledgments This work was supported by grants from NSF of China (grant no. 30800384); NSF of Anhui Province Department of Education (grant no. KJ2008B292); Scientific Research of BSKY (grant nos. XJ201106 and XJ200913) and Young Prominent Investigator Supporting Program from Anhui Medical University; Anhui Provincial Natural Science Foundation (11040606M171 and 1108085J11); and National Institutes of Health (NIH) of USA (5RO1DK079968-01A2m Ma).",

year = "2013",

month = dec,

doi = "10.1007/s11357-013-9511-5",

language = "English",

volume = "35",

pages = "2193--2202",

journal = "Age",

issn = "0161-9152",

publisher = "Springer Netherlands",

number = "6",

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TY - JOUR

T1 - Attenuated mesangial cell proliferation related to store-operated Ca 2+ entry in aged rat

T2 - The role of STIM 1 and Orai 1

AU - Shen, Bing

AU - Zhu, Jinhang

AU - Zhang, Jin

AU - Jiang, Feifei

AU - Wang, Zhaoyi

AU - Zhang, Yang

AU - Li, Jie

AU - Huang, Dake

AU - Ke, Daoping

AU - Ma, Rong

AU - Du, Juan

N1 - Funding Information: Acknowledgments This work was supported by grants from NSF of China (grant no. 30800384); NSF of Anhui Province Department of Education (grant no. KJ2008B292); Scientific Research of BSKY (grant nos. XJ201106 and XJ200913) and Young Prominent Investigator Supporting Program from Anhui Medical University; Anhui Provincial Natural Science Foundation (11040606M171 and 1108085J11); and National Institutes of Health (NIH) of USA (5RO1DK079968-01A2m Ma).

PY - 2013/12

Y1 - 2013/12

N2 - Store-operated Ca2+ entry (SOCE) is a common and ubiquitous mechanism regulating Ca2+ influx into cells and participates in numerous biological processes including cell proliferation. Glomerular mesangial cells (GMCs) play a role in the regulation of the glomerular filtration rate. From a clinical point of view, many physiological functions alter with age. In the present study, we used angiotensin II, glucagonand the sarco/endoplasmic reticulum membrane Ca2+ pump inhibitor thapsigargin to deplete the internal Ca2+ stores for the activation of SOCE. We found that SOCE was significantly attenuated in GMCs from aged (22-month-old) rats. The expression of SOCErelated components, stromal interaction molecule 1 (STIM 1) and Orai 1, in freshly isolated glomeruli notably decreased, and STIM 1 and Orai 1 puncta formation significantly reduced in primary-cultured GMCs in aged rats. Moreover, specific knockdown of STIM 1 and Orai 1 by small interfering RNA markedly suppressed SOCE and cell proliferation of GMCs isolated from young (3-month-old) rats. We conclude that the attenuation of GMCs proliferation can be attributed to the decreased SOCE partially caused by reduced expression of STIM 1 and Orai 1.

AB - Store-operated Ca2+ entry (SOCE) is a common and ubiquitous mechanism regulating Ca2+ influx into cells and participates in numerous biological processes including cell proliferation. Glomerular mesangial cells (GMCs) play a role in the regulation of the glomerular filtration rate. From a clinical point of view, many physiological functions alter with age. In the present study, we used angiotensin II, glucagonand the sarco/endoplasmic reticulum membrane Ca2+ pump inhibitor thapsigargin to deplete the internal Ca2+ stores for the activation of SOCE. We found that SOCE was significantly attenuated in GMCs from aged (22-month-old) rats. The expression of SOCErelated components, stromal interaction molecule 1 (STIM 1) and Orai 1, in freshly isolated glomeruli notably decreased, and STIM 1 and Orai 1 puncta formation significantly reduced in primary-cultured GMCs in aged rats. Moreover, specific knockdown of STIM 1 and Orai 1 by small interfering RNA markedly suppressed SOCE and cell proliferation of GMCs isolated from young (3-month-old) rats. We conclude that the attenuation of GMCs proliferation can be attributed to the decreased SOCE partially caused by reduced expression of STIM 1 and Orai 1.

KW - Aging

KW - Glomerular mesangial cell

KW - Orai 1

KW - Proliferation

KW - STIM 1

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U2 - 10.1007/s11357-013-9511-5

DO - 10.1007/s11357-013-9511-5

M3 - Article

C2 - 23334602

AN - SCOPUS:84892550526

SN - 0161-9152

VL - 35

SP - 2193

EP - 2202

JO - Age

JF - Age

IS - 6

ER -

Attenuated mesangial cell proliferation related to store-operated Ca ²⁺ entry in aged rat: The role of STIM 1 and Orai 1

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