Androgen Receptor-Mediated Regulation of Intracellular Calcium in Human Airway Smooth Muscle Cells

Rama Satyanarayana Raju Kalidhindi, Rathnavali Katragadda, Kerri L. Beauchamp, Christina M Pabelick, Y.s. Prakash, Venkatachalem Sathish

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)215-228
Number of pages14
JournalCellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
Volume53
Issue number1
DOIs
StatePublished - Jan 1 2019

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Keywords

  • Airway
  • Asthma
  • Contractility
  • Sex Difference
  • Sex Steroid
  • Testosterone

ASJC Scopus subject areas

  • Physiology

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