Downregulation of miR-140-3p Contributes to Upregulation of CD38 Protein in Bronchial Smooth Muscle Cells.
Downregulation of miR-140-3p Contributes to Upregulation of CD38 Protein in Bronchial Smooth Muscle Cells.
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DOI：
10.3390/ijms21217982
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发表时间：
2020-10-27
影响因子：
5.6
通讯作者：
Sakai H
中科院分区：
文献类型：
--
作者：
Chiba Y;Matsumoto M;Hanazaki M;Sakai H
在过敏性支气管哮喘中，气道平滑肌收缩性增加是气道高反应性（AHR）的原因之一。越来越多的证据也表明，microRNAs （miRNAs）可能参与气道疾病，包括哮喘，尽管它们在功能和病理中的作用在很大程度上未知。目前的研究旨在确定miRNA miR-140-3p在控制CD38蛋白表达中的作用，CD38被认为可以调节包括气道在内的平滑肌的收缩。在主动致敏和卵清蛋白抗原反复刺激的小鼠支气管平滑肌（BSMs）中，观察到CD38蛋白上调同时miR-140-3p显著降低。在培养的人BSM细胞（hBSMCs）中，转染合成的miR-140-3p抑制剂导致CD38蛋白升高，表明其基础蛋白表达受内源性miR-140-3p调节。用一种哮喘相关的细胞因子白细胞介素-13 （IL-13）治疗hBSMCs，导致CD38蛋白上调和miR-140-3p下调。用miR-140-3p模拟物转染hBSMCs可抑制IL-13诱导的CD38蛋白上调。另一方面，CD38产物环adp核糖（cADPR）及其拮抗剂8-溴-cADPR对BSM收缩没有影响，即使在抗原攻击小鼠中也是如此。综上所述，目前的研究结果表明，IL-13诱导的miR-140-3p下调可能导致该疾病BSM细胞中CD38蛋白的上调，尽管上调的CD38蛋白的功能和病理作用尚不清楚。
In allergic bronchial asthma, an increased smooth muscle contractility of the airways is one of the causes of the airway hyperresponsiveness (AHR). Increasing evidence also suggests a possible involvement of microRNAs (miRNAs) in airway diseases, including asthma, although their roles in function and pathology largely unknown. The current study aimed to determine the role of a miRNA, miR-140-3p, in the control of protein expression of CD38, which is believed to regulate the contraction of smooth muscles, including the airways. In bronchial smooth muscles (BSMs) of the mice that were actively sensitized and repeatedly challenged with ovalbumin antigen, an upregulation of CD38 protein concurrently with a significant reduction of miR-140-3p was observed. In cultured human BSM cells (hBSMCs), transfection with a synthetic miR-140-3p inhibitor caused an increase in CD38 protein, indicating that its basal protein expression is regulated by endogenous miR-140-3p. Treatment of the hBSMCs with interleukin-13 (IL-13), an asthma-related cytokine, caused both an upregulation of CD38 protein and a downregulation of miR-140-3p. Transfection of the hBSMCs with miR-140-3p mimic inhibited the CD38 protein upregulation induced by IL-13. On the other hand, neither a CD38 product cyclic ADP-ribose (cADPR) nor its antagonist 8-bromo-cADPR had an effect on the BSM contraction even in the antigen-challenged mice. Taken together, the current findings suggest that the downregulation of miR-140-3p induced by IL-13 might cause an upregulation of CD38 protein in BSM cells of the disease, although functional and pathological roles of the upregulated CD38 are still unclear.
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影响因子：
5.8
作者：
Chiba, Y;Ueno, A;Misawa, M
通讯作者：
Misawa, M
DOI：
10.1165/rcmb.2008-0163oc
发表时间：
2009-11-01
影响因子：
6.4
作者：
Chiba, Yoshihiko;Todoroki, Michiko;Misawa, Miwa
通讯作者：
Misawa, Miwa
影响因子：
14.9
作者：
Betel D;Wilson M;Gabow A;Marks DS;Sander C
通讯作者：
Sander C
DOI：
10.1165/rcmb.2004-0243oc
发表时间：
2005-02-01
影响因子：
6.4
作者：
Deshpande, DA;White, TA;Kannan, MS
通讯作者：
Kannan, MS
影响因子：
2.1
作者：
Guedes AG;Deshpande DA;Dileepan M;Walseth TF;Panettieri RA Jr;Subramanian S;Kannan MS
通讯作者：
Kannan MS