Effect of microRNA-22-3p on HMGB1/NLRP3 pathway of human lung microvascular endothelial cells_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

HE Binchan ^1,2 , XU Xiaoyong ¹ , MIN Haiyan ¹ ,  SU Xin ³

1. Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210019, P. R. China;
2. Department of Respiratory and Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210018, P. R. China;
3. Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210003, P. R. China;

Corresponding author：

SU Xin, Email: suxinjs@163.com

Keywords：

Acute respiratory distress syndrome; miR-22-3p; vascular endothelial cell; high mobility group box-1 protein; nucleotide binding oligomerization segment like receptor family 3

DOI：

10.7507/1671-6205.202206057

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Objective To investigate the effect of microRNA-22-3p (miR-22-3p) on the inflammation of human pulmonary microvascular endothelial cells (HPMEC) induced by lipopolysaccharide (LPS) by regulating the HMGB1/NLRP3 pathway. Methods miRNA microarray was taken from peripheral blood of patients with acute respiratory distress syndrome (ARDS) caused by abdominal infection and healthy controls for analysis, and the target miRNA was selected. miRNA mimics, inhibitor and their negative controls were transfected in HPMECs which were stimulated with LPS. Real time fluorescent quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to detect the mRNA and protein levels of high mobility group box-1 protein (HMGB1) and nucleotide binding oligomerization segment like receptor family 3 (NLRP3). RT-qPCR and enzyme linked immunosorbent assay were used to detect the levels of inflammatory factors in the cells and supernatant. Results miRNA microarray showed that miR-22-3p was down-regulated in the plasma of patients with ARDS. Compared with the negative control group, after miR-22-3p over-expression, the protein and mRNA levels of HMGB1 and NLRP3 decreased significantly. Similarly, the level of cleaved-caspase-1 decreased significantly. At the same time, interleukin (IL)-6, IL-8 and IL-1β mRNA level in cytoplasm and supernatant were down-regulated by miR-22-3p mimics. After transfected with miR-22-3p inhibitor, the expression levels of HMGB1, NLRP3, caspase-1 protein and inflammatory factors were significantly up-regulated. Conclusion miR-22-3p is significantly downregulated in peripheral blood of ARDS patients caused by abdominal infection, which can inhibit the expression of HMGB1 and NLRP3 and its downstream inflammatory response in HPMECs.

Citation： HE Binchan, XU Xiaoyong, MIN Haiyan, SU Xin. Effect of microRNA-22-3p on HMGB1/NLRP3 pathway of human lung microvascular endothelial cells. Chinese Journal of Respiratory and Critical Care Medicine, 2022, 21(12): 878-884. doi: 10.7507/1671-6205.202206057 Copy

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2.	Suzuki K, Okada H, Takemura G, et al. Recombinant thrombomodulin protects against LPS-induced acute respiratory distress syndrome via preservation of pulmonary endothelial glycocalyx. Br J Pharmacol, 2020, 177(17): 4021-4033.
3.	Gaboriaud C, Lorvellec M, Rossi V, et al. Complement system and alarmin HMGB1 crosstalk: for better or worse. Front Immunol, 2022, 13: 869720.
4.	Li RT, Zhang JC, Pan SW, et al. HMGB1 aggravates lipopolysaccharide-induced acute lung injury through suppressing the activity and function of Tregs. Cell Immunol, 2020, 356: 104192.
5.	Jabaudon M, Blondonnet R, Roszyk L, et al. Soluble forms and ligands of the receptor for advanced glycation end-products in patients with acute respiratory distress syndrome: an observational prospective study. PLoS One, 2015, 10(8): e0135857.
6.	Nakamura T, Sato E, Fujiwara N, et al. Increased levels of soluble receptor for advanced glycation end products (sRAGE) and high mobility group box 1 (HMGB1) are associated with death in patients with acute respiratory distress syndrome. Clin Biochem, 2011, 44(8-9): 601-604.
7.	Yang XY, Cheng XY, Tang YT, et al. The role of type 1 interferons in coagulation induced by gram-negative bacteria. Blood, 2020, 135(14): 1087-1100.
8.	Wang HL, Tsao SM, Yeh CB, et al. Circulating level of high mobility group box-1 predicts the severity of community-acquired pneumonia: regulation of inflammatory responses via the c-Jun N-terminal signaling pathway in macrophages. Mol Med Rep, 2017, 16(3): 2361-2366.
9.	Ueno H, Matsuda T, Hashimoto S, et al. Contributions of high mobility group box protein in experimental and clinical acute lung injury. Am J Respir Crit Care Med, 2004, 170(12): 1310-1316.
10.	Gu JR, Ran XF, Deng J, et al. Glycyrrhizin alleviates sepsis-induced acute respiratory distress syndrome via suppressing of HMGB1/TLR9 pathways and neutrophils extracellular traps formation. Int Immunopharmacol, 2022, 108: 108730.
11.	Xian HX, Liu Y, Rundberg Nilsson A, et al. Metformin inhibition of mitochondrial ATP and DNA synthesis abrogates NLRP3 inflammasome activation and pulmonary inflammation. Immunity, 2021, 54(7): 1463-1477. e11.
12.	Huang Y, Xu W, Zhou RB. NLRP3 inflammasome activation and cell death. Cell Mol Immunol, 2021, 18(9): 2114-2127.
13.	Wang S, Zhao JJ, Wang HY, et al. Blockage of P2X7 attenuates acute lung injury in mice by inhibiting NLRP3 inflammasome. Int Immunopharmacol, 2015, 27(1): 38-45.
14.	Lu TX, Rothenberg ME. MicroRNA. J Allergy Clin Immunol, 2018, 141(4): 1202-1207.
15.	Jankauskaite L, Malinauskas M, Mickeviciute GC. HMGB1: a potential target of nervus vagus stimulation in pediatric SARS-CoV-2-induced ALI/ARDS. Front Pediatr, 2022, 10: 884539.
16.	Zhang Y, Liu X, Bai X, et al. Melatonin prevents endothelial cell pyroptosis via regulation of long noncoding RNA MEG3/miR-223/NLRP3 axis. J Pineal Res, 2018, 64(2): e12449.
17.	He BC, Zhou W, Rui YW, et al. MicroRNA-574-5p attenuates acute respiratory distress syndrome by targeting HMGB1. Am J Respir Cell Mol Biol, 2021, 64(2): 196-207.
18.	胡博, 栾正刚. 普通肝素改善高迁移率族蛋白1介导的血管内皮细胞屏障通透性增加的实验研究. 中国呼吸与危重监护杂志, 2017, 16(1): 29-33.
19.	罗亚岚, 许才明, 李兆霞, 等. NLRP3炎性小体—急性肺损伤的发病核心. 中国急救医学, 2019, 39(3): 285-289.
20.	汤建华, 刘建华, 徐涛, 等. 微RNA-203通过TLR4/NF-κB/NLRP3通路保护肺泡上皮细胞免受脂多糖诱导损伤. 中国呼吸与危重监护杂志, 2022, 21(6): 425-431.
21.	Kim EJ, Park SY, Baek SE, et al. HMGB1 increases IL-1β production in vascular smooth muscle cells via NLRP3 inflammasome. Front Physiol, 2018, 9: 313.
22.	Bui FQ, Johnson L, Roberts J, et al. Fusobacterium nucleatum infection of gingival epithelial cells leads to NLRP3 inflammasome-dependent secretion of IL-1β and the danger signals ASC and HMGB1. Cell Microbiol, 2016, 18(7): 970-981.
23.	Feng XD, Luo QQ, Wang H, et al. MicroRNA-22 suppresses cell proliferation, migration and invasion in oral squamous cell carcinoma by targeting NLRP3. J Cell Physiol, 2018, 233(9): 6705-6713.
24.	Li S, Liang X, Ma L, et al. MiR-22 sustains NLRP3 expression and attenuates H. pylori-induced gastric carcinogenesis. Oncogene, 2018, 37(7): 884-896.
25.	Zhang J, Chen Q, Dai ZQ, et al. miR-22 alleviates sepsis-induced acute kidney injury via targeting the HMGB1/TLR4/NF-κB signaling pathway[J/OL]. Int Urol Nephrol, 2022.
26.	Zhang DY, Zou XJ, Cao CH, et al. Identification and functional characterization of long non-coding RNA MIR22HG as a tumor suppressor for hepatocellular carcinoma. Theranostics, 2018, 8(14): 3751-3765.
27.	Pelosi P, D'Onofrio D, Chiumello D, et al. Pulmonary and extrapulmonary acute respiratory distress syndrome are different. Eur Respir J Suppl, 2003, 42: 48s-56s.
28.	Peng JY, Jin JY, Su WR, et al. High-mobility group box 1 inhibitor BoxA alleviates neuroinflammation-induced retinal ganglion cell damage in traumatic optic neuropathy. Int J Mol Sci, 2022, 23(12): 6715.
29.	Zhang KM, Fan C, Cai DP, et al. Contribution of TGF-beta-mediated NLRP3-HMGB1 activation to tubulointerstitial fibrosis in rat with angiotensin II-induced chronic kidney disease. Front Cell Dev Biol, 2020, 8: 1.

1. Villar J, Blanco J, Kacmarek RM. Current incidence and outcome of the acute respiratory distress syndrome. Curr Opin Crit Care, 2016, 22(1): 1-6.
2. Suzuki K, Okada H, Takemura G, et al. Recombinant thrombomodulin protects against LPS-induced acute respiratory distress syndrome via preservation of pulmonary endothelial glycocalyx. Br J Pharmacol, 2020, 177(17): 4021-4033.
3. Gaboriaud C, Lorvellec M, Rossi V, et al. Complement system and alarmin HMGB1 crosstalk: for better or worse. Front Immunol, 2022, 13: 869720.
4. Li RT, Zhang JC, Pan SW, et al. HMGB1 aggravates lipopolysaccharide-induced acute lung injury through suppressing the activity and function of Tregs. Cell Immunol, 2020, 356: 104192.
5. Jabaudon M, Blondonnet R, Roszyk L, et al. Soluble forms and ligands of the receptor for advanced glycation end-products in patients with acute respiratory distress syndrome: an observational prospective study. PLoS One, 2015, 10(8): e0135857.
6. Nakamura T, Sato E, Fujiwara N, et al. Increased levels of soluble receptor for advanced glycation end products (sRAGE) and high mobility group box 1 (HMGB1) are associated with death in patients with acute respiratory distress syndrome. Clin Biochem, 2011, 44(8-9): 601-604.
7. Yang XY, Cheng XY, Tang YT, et al. The role of type 1 interferons in coagulation induced by gram-negative bacteria. Blood, 2020, 135(14): 1087-1100.
8. Wang HL, Tsao SM, Yeh CB, et al. Circulating level of high mobility group box-1 predicts the severity of community-acquired pneumonia: regulation of inflammatory responses via the c-Jun N-terminal signaling pathway in macrophages. Mol Med Rep, 2017, 16(3): 2361-2366.
9. Ueno H, Matsuda T, Hashimoto S, et al. Contributions of high mobility group box protein in experimental and clinical acute lung injury. Am J Respir Crit Care Med, 2004, 170(12): 1310-1316.
10. Gu JR, Ran XF, Deng J, et al. Glycyrrhizin alleviates sepsis-induced acute respiratory distress syndrome via suppressing of HMGB1/TLR9 pathways and neutrophils extracellular traps formation. Int Immunopharmacol, 2022, 108: 108730.
11. Xian HX, Liu Y, Rundberg Nilsson A, et al. Metformin inhibition of mitochondrial ATP and DNA synthesis abrogates NLRP3 inflammasome activation and pulmonary inflammation. Immunity, 2021, 54(7): 1463-1477. e11.
12. Huang Y, Xu W, Zhou RB. NLRP3 inflammasome activation and cell death. Cell Mol Immunol, 2021, 18(9): 2114-2127.
13. Wang S, Zhao JJ, Wang HY, et al. Blockage of P2X7 attenuates acute lung injury in mice by inhibiting NLRP3 inflammasome. Int Immunopharmacol, 2015, 27(1): 38-45.
14. Lu TX, Rothenberg ME. MicroRNA. J Allergy Clin Immunol, 2018, 141(4): 1202-1207.
15. Jankauskaite L, Malinauskas M, Mickeviciute GC. HMGB1: a potential target of nervus vagus stimulation in pediatric SARS-CoV-2-induced ALI/ARDS. Front Pediatr, 2022, 10: 884539.
16. Zhang Y, Liu X, Bai X, et al. Melatonin prevents endothelial cell pyroptosis via regulation of long noncoding RNA MEG3/miR-223/NLRP3 axis. J Pineal Res, 2018, 64(2): e12449.
17. He BC, Zhou W, Rui YW, et al. MicroRNA-574-5p attenuates acute respiratory distress syndrome by targeting HMGB1. Am J Respir Cell Mol Biol, 2021, 64(2): 196-207.
18. 胡博, 栾正刚. 普通肝素改善高迁移率族蛋白1介导的血管内皮细胞屏障通透性增加的实验研究. 中国呼吸与危重监护杂志, 2017, 16(1): 29-33.
19. 罗亚岚, 许才明, 李兆霞, 等. NLRP3炎性小体—急性肺损伤的发病核心. 中国急救医学, 2019, 39(3): 285-289.
20. 汤建华, 刘建华, 徐涛, 等. 微RNA-203通过TLR4/NF-κB/NLRP3通路保护肺泡上皮细胞免受脂多糖诱导损伤. 中国呼吸与危重监护杂志, 2022, 21(6): 425-431.
21. Kim EJ, Park SY, Baek SE, et al. HMGB1 increases IL-1β production in vascular smooth muscle cells via NLRP3 inflammasome. Front Physiol, 2018, 9: 313.
22. Bui FQ, Johnson L, Roberts J, et al. Fusobacterium nucleatum infection of gingival epithelial cells leads to NLRP3 inflammasome-dependent secretion of IL-1β and the danger signals ASC and HMGB1. Cell Microbiol, 2016, 18(7): 970-981.
23. Feng XD, Luo QQ, Wang H, et al. MicroRNA-22 suppresses cell proliferation, migration and invasion in oral squamous cell carcinoma by targeting NLRP3. J Cell Physiol, 2018, 233(9): 6705-6713.
24. Li S, Liang X, Ma L, et al. MiR-22 sustains NLRP3 expression and attenuates H. pylori-induced gastric carcinogenesis. Oncogene, 2018, 37(7): 884-896.
25. Zhang J, Chen Q, Dai ZQ, et al. miR-22 alleviates sepsis-induced acute kidney injury via targeting the HMGB1/TLR4/NF-κB signaling pathway[J/OL]. Int Urol Nephrol, 2022.
26. Zhang DY, Zou XJ, Cao CH, et al. Identification and functional characterization of long non-coding RNA MIR22HG as a tumor suppressor for hepatocellular carcinoma. Theranostics, 2018, 8(14): 3751-3765.
27. Pelosi P, D'Onofrio D, Chiumello D, et al. Pulmonary and extrapulmonary acute respiratory distress syndrome are different. Eur Respir J Suppl, 2003, 42: 48s-56s.
28. Peng JY, Jin JY, Su WR, et al. High-mobility group box 1 inhibitor BoxA alleviates neuroinflammation-induced retinal ganglion cell damage in traumatic optic neuropathy. Int J Mol Sci, 2022, 23(12): 6715.
29. Zhang KM, Fan C, Cai DP, et al. Contribution of TGF-beta-mediated NLRP3-HMGB1 activation to tubulointerstitial fibrosis in rat with angiotensin II-induced chronic kidney disease. Front Cell Dev Biol, 2020, 8: 1.

Chinese Journal of Respiratory and Critical Care Medicine

Effect of microRNA-22-3p on HMGB1/NLRP3 pathway of human lung microvascular endothelial cells

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