雄激素受体
细胞内
哮喘
内分泌学
内科学
生物学中的钙
炎症
收缩性
受体
医学
雄激素
下调和上调
污渍
化学
生物
细胞生物学
激素
癌症
前列腺癌
基因
生物化学
作者
Raj Satyanarayana,Rama Satyanarayana Raju Kalidhindi,Rathnavali Katragadda,Kerri Beauchamp,Y. S. Prakash,Venkatachalem Sathish,NULL AUTHOR_ID,NULL AUTHOR_ID
摘要
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.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.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.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.
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