TY - JOUR
T1 - Androgen receptor-mediated regulation of intracellular calcium in human airway smooth muscle cells
AU - Kalidhindi, Rama Satyanarayana Raju
AU - Katragadda, Rathnavali
AU - Beauchamp, Kerri L.
AU - Pabelick, Christina M.
AU - Prakash, Y. S.
AU - Sathish, Venkatachalem
N1 - Funding Information:
This study was supported by NIH Grants R01-HL123494 and R01-HL123494-02S1 (Venkatachalem), R01-HL088029 (Prakash), R01-HL142061 (Pabelick, Prakash) ND EPSCoR with NSF#1355466 and NDSU RCA.
Publisher Copyright:
© 2019 The Author(s).
PY - 2019
Y1 - 2019
N2 - Background/Aims: With the prevalence of asthma being greater in women, detrimental effects of female sex steroids have been explored, but potential protective effects of androgens are not established. Airway smooth muscle (ASM) is a key cell type in contractility and remodelling of asthma. There are no data on expression and functionality of androgen receptor (AR) in human ASM cells. Methods: We used primary human ASM cells from non-asthmatics vs. asthmatics to determine AR expression at baseline and with inflammation measured using Western blotting/qRT-PCR, and the role of AR in regulating intracellular Ca2+ ([Ca2+]i) measured using Fluo-3 loaded real time [Ca2+]i imaging. Results: We found that compared to females, baseline AR is greater in male ASM and increases with inflammation/asthma. Androgens, via AR, blunted TNFα or IL-13-induced enhancement of ASM [Ca2+]i in both males and females, with retained efficacy in asthmatics. AR effects involve reduced Ca2+ influx via L-type channels and store-operated Ca2+ entry, the latter by downregulating STIM1 and Orai1 and increasing TMEM66. Conclusion: Our data show AR expression is increased in female ASM with asthma, but has retained functionality that could be used to reduce [Ca2+]i towards alleviating airway hyperresponsiveness.
AB - Background/Aims: With the prevalence of asthma being greater in women, detrimental effects of female sex steroids have been explored, but potential protective effects of androgens are not established. Airway smooth muscle (ASM) is a key cell type in contractility and remodelling of asthma. There are no data on expression and functionality of androgen receptor (AR) in human ASM cells. Methods: We used primary human ASM cells from non-asthmatics vs. asthmatics to determine AR expression at baseline and with inflammation measured using Western blotting/qRT-PCR, and the role of AR in regulating intracellular Ca2+ ([Ca2+]i) measured using Fluo-3 loaded real time [Ca2+]i imaging. Results: We found that compared to females, baseline AR is greater in male ASM and increases with inflammation/asthma. Androgens, via AR, blunted TNFα or IL-13-induced enhancement of ASM [Ca2+]i in both males and females, with retained efficacy in asthmatics. AR effects involve reduced Ca2+ influx via L-type channels and store-operated Ca2+ entry, the latter by downregulating STIM1 and Orai1 and increasing TMEM66. Conclusion: Our data show AR expression is increased in female ASM with asthma, but has retained functionality that could be used to reduce [Ca2+]i towards alleviating airway hyperresponsiveness.
KW - Airway
KW - Asthma
KW - Contractility
KW - Sex difference
KW - Sex steroid
KW - Testosterone
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U2 - 10.33594/000000131
DO - 10.33594/000000131
M3 - Article
C2 - 31299143
AN - SCOPUS:85069808931
SN - 1015-8987
VL - 53
SP - 215
EP - 228
JO - Cellular Physiology and Biochemistry
JF - Cellular Physiology and Biochemistry
IS - 1
ER -