RGS2 attenuates alveolar macrophage damage by inhibiting the Gq/ 11-Ca2+ pathway during cowshed PM2.5 exposure, and aberrant RGS2 expression is associated with TLR2/4 activation
文献类型： 外文期刊
作者： Ma, Zhenhua 1 ; Du, Xiaohui 1 ; Sun, Yize 1 ; Sun, Ke 1 ; Zhang, Xiqing 1 ; Wang, Lixia 2 ; Zhu, Yanbin 3 ; Basang, Wangdui 3 ; Gao, Yunhang 1 ;
作者机构： 1.Jilin Agr Univ, Coll Anim Sci & Technol, Dept Vet Med, Changchun 130118, Peoples R China
2.Chinese Acad Sci, Northeast Inst Geog & Agroecol, Changchun 130102, Peoples R China
3.Tibet Acad Agr & Anim Husb Sci, Inst Anim Husb & Vet Med, Lhasa 850009, Peoples R China
关键词： Fine particulate matter; Cowshed; Intracellular Ca2+; Regulator of G-protein signaling 2; Gq/11; PLC beta/IP3R
期刊名称：TOXICOLOGY AND APPLIED PHARMACOLOGY （ 影响因子：3.3； 五年影响因子：3.6 ）
ISSN： 0041-008X
年卷期： 2024 年 487 卷
页码：
收录情况： SCI
摘要： Staff and animals in livestock buildings are constantly exposed to fine particulate matter (PM2.5), which affects their respiratory health. However, its exact pathogenic mechanism remains unclear. Regulator of G-protein signaling 2 (RGS2) has been reported to play a regulatory role in pneumonia. The aim of this study was to explore the therapeutic potential of RGS2 in cowshed PM2.5-induced respiratory damage. PM2.5 was collected from a cattle farm, and the alveolar macrophages (NR8383) of the model animal rat were stimulated with different treatment conditions of cowshed PM2.5. The RGS2 overexpression vector was constructed and transfected it into cells. Compared with the control group, cowshed PM2.5 significantly induced a decrease in cell viability and increased the levels of apoptosis and proinflammatory factor expression. Overexpression of RGS2 ameliorated the above-mentioned cellular changes induced by cowshed PM2.5. In addition, PM2.5 has significantly induced intracellular Ca2+ dysregulation. Affinity inhibition of Gq/11 by RGS2 attenuated the cytosolic calcium signaling pathway mediated by PLC beta/IP3R. To further investigate the causes and mechanisms of action of differential RGS2 expression, the possible effects of oxidative stress and TLR2/4 activation were investigated. The results have shown that RGS2 expression was not only regulated by oxidative stress-induced nitric oxide during cowshed PM2.5 cells stimulation but the activation of TLR2/4 had also an important inhibitory effect on its protein expression. The present study demonstrates the intracellular Ca2+ regulatory role of RGS2 during cellular injury, which could be a potential target for the prevention and treatment of PM2.5-induced respiratory injury.
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