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Original Research

Open Access

ANXA3 regulates HIF1α-induced NLRP3 inflammasome activity and promotes LPS-induced inflammatory response in bronchial epithelial cells

  • Shenrong Zhang1
  • Qimin Shao1
  • Lihong Jia1
  • Fang Zhou1

1Department of Rheumatology & Immunology, Nephrology, Hangzhou Children’s Hospital, 310014 Hangzhou City, Zhejiang Province, China

DOI: 10.22514/sv.2021.078 Vol.17,Issue 3,May 2021 pp.206-213

Submitted: 20 February 2021 Accepted: 06 April 2021

Published: 08 May 2021

*Corresponding Author(s): Qimin Shao E-mail:


Introduction: Childhood asthma is one of the most common pediatric diseases, and its incidence is increasing. Annexin A3 (ANXA3) is a member of the Annexin family, a well-known polygenic family of membrane binding proteins. Bioinformation analysis showed that ANXA3 was highly expressed in asthmatic patients, suggesting the effects of ANXA3 on asthma, whereas the mechanism is still unclear.

Methods: A inflammatory response model of bronchial epithelial BEAS-2B cells induced by LPS was constructed. Immunoblot and quantitative PCR assays were performed to detect the expression levels of ANXA3 in control or LPS-induced BEAS-2B cells. MTT, flow cytometry (FCM), and Immunoblot assays were respectively conducted to detect the effects of ANXA3 on survival and apoptosis of LPS-induced BEAS-2B cells. qPCR and ELISA assays were performed to detect the expression of TNF-α, IL-6, and IL-8. Additionally, Immunoblot assays were performed to detect the effects of ANXA3 on HIF1α and NLRP3 inflammasome in BEAS-2B cells.

Results: We found ANXA3 was overexpressed in LPS-induced BEAS-2B cells. ANXA3 ablation promoted the survival of LPS-induced BEAS-2B cells and suppressed the inflammatory response of LPS-induced BEAS-2B cells. Importantly, we noticed ANXA3 inhibited HIF1α-induced NLRP3 inflammasome activity, and increasing the expression of HIF-α rescued the effects of ANXA3 depletion on asthma.

Conclusion: ANXA3 enhanced LPS-triggered inflammation of human bronchial epithelial cells by regulating hypoxia-inducible factor-1α (HIF1α)-mediated NLRP3 inflammasome activation, and thought ANXA3 as a promising molecular target for acute asthma treatment.


Annexin A3 (ANXA3); Acute asthma; Inflammatory response; NLRP3 inflammasome; Hypoxia-inducible factor-1α (HIF1α)

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Shenrong Zhang,Qimin Shao,Lihong Jia,Fang Zhou. ANXA3 regulates HIF1α-induced NLRP3 inflammasome activity and promotes LPS-induced inflammatory response in bronchial epithelial cells. Signa Vitae. 2021. 17(3);206-213.


[1] Krasilnikova SV, Khramov AA, Khramova RN, Ovsyannikov DY, Daniel-Abu MI, Novozhilov A, et al. The Relationship between indicators of nasal respiratory function and spirometric parameters in children with bronchial asthma. Frontiers in Pediatrics. 2021; 8: 580043.

[2] Huo R, Tian X, Chang Q, Liu D, Wang C, Bai J, et al. Targeted inhibition of β-catenin alleviates airway inflammation and remodeling in asthma via modulating the profibrotic and anti-inflammatory actions of transforming growth factor-β1. Therapeutic Advances in Respiratory Disease. 2021; 15: 1753466620981858.

[3] Galbraith AA, Ross-Degnan D, Zhang F, Wu AC, Sinaiko A, LeCates RF, et al. Association of controller use and exacerbations for high-deductible plan enrollees with and without family members with asthma. Annals of the American Thoracic Society. 2021.

[4] Tirpude NV, Sharma A, Joshi R, Kumari M, Acharya V. Vi-tex negundo Linn. Extract alleviates inflammatory aggravation and lung injury by modulating AMPK/PI3K/Akt/p38-NF-κB and TGF-β/Smad/Bcl2/caspase/LC3 cascade and macrophages activation in murine model of OVA-LPS induced allergic asthma. Journal of Ethnopharmacology. 2021; 271: 113894.

[5] DiVito B, Talavlikar R, Seifu S. Common hematologic, nutritional, asthma/allergic conditions and lead screening/management. Primary Care: Clinics in Office Practice. 2021; 48: 67–81.

[6] Wang J, Jia X, Meng X, Li Y, Wu W, Zhang X, et al. Annexin A3 may play an important role in ochratoxin-induced malignant transformation of human gastric epithelium cells. Toxicology Letters. 2019; 313: 150–158.

[7] Xu B, Zhang X, Gao Y, Song J, Shi B. Microglial Annexin A3 promoted the development of melanoma via activation of hypoxia-inducible factor-1alpha/vascular endothelial growth factor signaling pathway. Journal of Clinical Laboratory Analysis. 2021; 35: e23622.

[8] Pan QZ, Pan K, Weng DS, Zhao JJ, Zhang XF, Wang DD, et al. Annexin A3 promotes tumorigenesis and resistance to chemotherapy in hepatocellular carcinoma. Molecular Carcinogenesis. 2015; 54: 598–607.

[9] Pan Q, Pan K, Wang Q, Weng D, Zhao J, Zheng H, et al. Annexin A3 as a potential target for immunotherapy of liver cancer stem-like cells. Stem Cells. 2015; 33: 354–366.

[10] Xu R, Yin J, Zhang Y, Zhang S. Annexin A3 depletion overcomes resistance to oxaliplatin in colorectal cancer via the MAPK signaling pathway. Journal of Cellular Biochemistry. 2019; 120: 14585–14593.

[11] Wu N, Liu S, Guo C, Hou Z, Sun M. The role of Annexin A3 playing in cancers. Clinical and Translational Oncology. 2013; 15: 106–110.

[12] Zhang Z, Deng M, Huang J, Wu J, Li Z, Xing M, et al. Microglial Annexin A3 downregulation alleviates bone cancer-induced pain through inhibiting the HIFf-1α/vascular endothelial growth factor signaling pathway. Pain. 2020; 161: 2750–2762.

[13] Ma XL, Jiang M, Zhao Y, Wang BL, Shen MN, Zhou Y, et al. Application of serum Annexin A3 in diagnosis, outcome prediction and therapeutic response evaluation for patients with hepatocellular carcinoma. Annals of Surgical Oncology. 2018; 25: 1686–1694.

[14] Xie Y, Fu D, He Z, Tan Q. Prognostic value of Annexin A3 in human colorectal cancer and its correlation with hypoxia-inducible factor-1α. Oncology Letters. 2013; 6: 1631–1635.

[15] Chaudhuri R, Rubin A, Sumino K, Lapa E Silva JR, Niven R, Siddiqui S, et al. Safety and effectiveness of bronchial thermoplasty after 10 years in patients with persistent asthma (BT10+): a follow-up of three randomised controlled trials. The Lancet Respiratory Medicine. 2021; S2213-2600(20)30408-2.

[16] Nakamura N, Kashitani Y, Yoshisue H, Nagasaki M, Sasajima T. Real-life long-term safety and effectiveness of omalizumab in Japanese pediatric patients with severe allergic asthma: a post-marketing surveillance. Allergology International. 2021; S1323-8930(21)00001-0.

[17] Meadows SM, Cleaver O. Annexin A3 regulates early blood vessel formation. PLoS ONE. 2015; 10: e0132580.

[18] Liu YF, Liu QQ, Zhang YH, Qiu JH. Annexin A3 knockdown suppresses lung adenocarcinoma. Analytical Cellular Pathology. 2016; 2016: 4131403.

[19] Bombelli S, Torsello B, De Marco S, Lucarelli G, Cifola I, Grasselli C, et al. 36-kDa Annexin A3 isoform negatively modulates lipid storage in clear cell renal cell carcinoma cells. The American Journal of Pathology. 2020; 190: 2317–2326.

[20] Watanabe T, Ito Y, Sato A, Hosono T, Niimi S, Ariga T, et al. Annexin A3 as a negative regulator of adipocyte differentiation. Journal of Biochemistry. 2012; 152: 355–363.

[21] Huang K, Crist AM, Patel NR, Blanks A, Carter K, Cleaver O, et al. Annexin A3 is necessary for parallel artery-vein alignment in the mouse retina. Developmental Dynamics. 2020; 249: 666–678.

[22] Hughes D. Childhood asthma and school. Paediatrics & Child Health. 2021; 26: e4–e5.

[23] Jiang A, Zhang Y, Zhang X, Wu D, Liu Z, Li S, et al. Morin alleviates LPS-induced mastitis by inhibiting the PI3K/AKT, MAPK, NF-κB and NLRP3 signaling pathway and protecting the integrity of blood-milk barrier. International Immunopharmacology. 2020; 78: 105972.

[24] Yu S, Liu X, Yu D, Changyong E, Yang J. Morin protects LPS-induced mastitis via inhibiting NLRP3 inflammasome and NF-κB signaling pathways. Inflammation. 2020; 43: 1293–1303.

[25] Xu R, Yin J, Zhang Y, Zhang S. Annexin A3 depletion overcomes resistance to oxaliplatin in colorectal cancer via the MAPK signaling pathway. Journal of Cellular Biochemistry. 2019; 120: 14585–14593.

[26] Wang Y, Wang C, Yang Q, Cheng YL. ANXA3 Silencing Ameliorates Intracranial Aneurysm via Inhibition of the JNK Signaling Pathway. Molecular Therapy—Nucleic Acids. 2019; 17: 540–550.

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