Mechanism of calcium-sensing receptor regulating macrophage polariza-tion in hypertensive rats
10.3969/j.issn.1000-4718.2025.04.001
- VernacularTitle:钙敏感受体调控高血压大鼠巨噬细胞极化的机制研究
- Author:
Xiaofang YANG
1
;
Lijuan HE
;
Na TANG
;
Lamei WANG
;
Yuanyuan QU
;
Hua ZHONG
;
Qiang ZHANG
;
Fengmei DENG
;
Bin TANG
;
Dongmei XI
;
Fang HE
Author Information
1. 石河子大学医学院新疆地方与民族高发病教育部重点实验室,石河子大学医学院第一附属医院国家卫健委中亚高发病防治重点实验室,石河子大学医学院病理生理学教研室,新疆 石河子 832000
- Publication Type:Journal Article
- Keywords:
essential hypertension;
calcium-sensing receptor;
macrophage polarization;
NLRP3 inflammasome
- From:
Chinese Journal of Pathophysiology
2025;41(4):625-636
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To explore the role and mechanism of calcium-sensing receptor(CaSR)in regulating macro-phage polarization in hypertensive rats.METHODS:Male spontaneously hypertensive rats(SHR)and Wistar-Kyoto(WKY)rats were categorized into WKY group,SHR group,SHR+R568(CaSR agonist)group,and SHR+NPS2143(CaSR inhibitor)group.The thoracic aorta was isolated,and the expression of CaSR and macrophage polarization markers in the aorta was observed through immunofluorescence staining.The primary peritoneal macrophages of SHR and WKY rats were aseptically extracted following anesthesia.After intervention with R568 and NPS2143,the expression levels of M1 and M2 markers of peritoneal macrophages were observed by Western blot and immunofluorescence staining.The levels of interleukin(IL)-1β and IL-10 were measured by ELISA.The concentration of Ca2+in peritoneal macrophages was mea-sured by immunofluorescence.Western blot was employed to identify the expression of CaSR and nucleotide-binding oligo-merization domain-like receptor protein 3(NLRP3)inflammasome components.Following anesthesia,vascular smooth muscle cells(VSMCs)were isolated from SHR using an adherent method.Subsequently,a co-culture system was estab-lished with macrophage supernatant.The optimal action time for this co-culture system was determined through CCK-8 as-say.RESULTS:Compared with SHR group,activation of CaSR resulted in a significant decrease in the protein expres-sion of M1 polarization markers(P<0.05)and a concomitant increase in the protein expression of M2 polarization markers in the aorta(P<0.05).Compared with SHR group,administration of R568 led to a significant decrease in the protein ex-pression of M1 polarization markers(P<0.05)and a concomitant increase in the protein expression of M2 polarization markers(P<0.05)in peritoneal macrophages.Additionally,there was a notable reduction in the protein levels of NLRP3 inflammasome components(P<0.05).Furthermore,the fluorescence intensity of intracellular Ca2+was significantly en-hanced following R568 treatment(P<0.05).After administration of MCC950,an NLRP3 inflammasome inhibitor,the re-sults were consistent with those observed following R568 treatment,demonstrating statistical significance(P<0.05).This effect was reversed by the combined intervention of U73122,a phospholipase C(PLC)inhibitor(P<0.05).Compared with the control(0 h),the 24-h peritoneal macrophage supernatant exhibited the strongest capacity to enhance the viabili-ty of VSMCs after 24 h of culture(P<0.05).CONCLUSION:In hypertensive rats,the CaSR inhibits NLRP3 inflamma-some activation via the PLC-Ca2+signaling pathway,thereby mediating an increase in macrophage polarization towards the M2 phenotype and a decrease towards the M1 phenotype.
