Inhibition of heat shock protein family A member 8 attenuates spinal cord ischemia-reperfusion injury via astrocyte NF-kappa B/NLRP3 inflammasome pathway HSPA8 inhibition protects spinal ischemia-reperfusion injury

Mi, Jingyi1; Yang, Yang2; Yao, Hao3; Huan, Zhirong3; Xu, Ce3; Ren, Zhiheng4; Li, Wenfu4; Tang, Ying5,6,7; Fu, Rao4; Ge, Xin3,8

2021-08-06

10.1186/s12974-021-02220-0

JOURNAL OF NEUROINFLAMMATION   影响因子和分区

1742-2094

["Background: Astrocyte over-activation and extensive neuron loss are the main characteristic pathological features of spinal cord ischemia-reperfusion injury (SCII). Prior studies have placed substantial emphasis on the role of heat shock protein family A member 8 (HSPA8) on postischemic myocardial inflammation and cardiac dysfunction. However, it has never been determined whether HSPA8 participates in astrocyte activation and thus mediated neuroinflammation associated with SCII.","Methods: The left renal artery ligation-induced SCII rat models and oxygen-glucose deprivation and reoxygenation (OGD/R)-induced rat primary cultured astrocytes were established. The lentiviral vector encoding short hairpin RNA targeting HSPA8 was delivered to the spinal cord by intrathecal administration or to culture astrocytes. Then, the spinal neuron survival, gliosis, and nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome and its related pro-inflammatory cytokines were analyzed.","Results: SCII significantly enhanced the GFAP and HSPA8 expression in the spinal cord, resulting in blood-brain barrier breakdown and the dramatical loss of spinal neuron and motor function. Moreover, injury also increased spinal nuclear factor-kappa B (NF-kappa B) p65 phosphorylation, NLRP3 inflammasome-mediated caspase-1 activation, and subsequent interleukin (IL)-1 beta as well as IL-18 secretion. Silencing the HSPA8 expression efficiently ameliorated the spinal cord tissue damage and promoted motor function recovery after SCII, through blockade of the astrocyte activation and levels of phosphorylated NF-kappa B, NLRP3, caspase-1, IL-1 beta, and IL-18. Further in vitro studies confirmed that HSPA8 knockdown protected astrocytes from OGD/R-induced injury via the blockade of NF-kappa B and NLRP3 inflammasome activation.","Conclusion: Our findings indicate that knockdown of HSPA8 inhibits spinal astrocytic damage after SCII, which may provide a promising therapeutic strategy for SCII treatment."]

HSPA8 Spinal cord ischemia-reperfusion injury Astrocyte Neuroinflammation NF-kappa B NLRP3

SCI

英语

其他

National Natural Science Foundation of China[82071496] ; Young Teacher Foundation of Sun Yat-sen University[59000-18841219] ; Natural Science Foundation of Guangdong Province[2021A1515010463] ; Precision Medicine Projects of the Wuxi Municipal Healthy Commission[J202007]

Immunology ; Neurosciences & Neurology

Immunology ; Neurosciences

WOS:000682476400001

BMC

Web of Science

1.Soochow Univ, Dept Sports Med, Wuxi Affiliated Hosp 9, Wuxi 214000, Jiangsu, Peoples R China
2.Cent Hosp Jinzhou, Dept Neurosurg, Jinzhou 121001, Liaoning, Peoples R China
3.Soochow Univ, Dept ICU, Wuxi Affiliated Hosp 9, Wuxi 214000, Jiangsu, Peoples R China
4.Sun Yat Sen Univ, Dept Anat, Sch Med, Guangzhou 510080, Guangdong, Peoples R China
5.Rutgers State Univ, Dept Microbiol Biochem & Mol Genet, New Jersey Med Sch, Newark, NJ 07103 USA
6.Southern Univ Sci & Technol, Brain Res Ctr, Shenzhen 518055, Guangdong, Peoples R China
7.Southern Univ Sci & Technol, Dept Biol, Shenzhen 518055, Guangdong, Peoples R China
8.Orthoped Inst Wuxi City, Wuxi 214000, Jiangsu, Peoples R China

Mi, Jingyi,Yang, Yang,Yao, Hao,et al. Inhibition of heat shock protein family A member 8 attenuates spinal cord ischemia-reperfusion injury via astrocyte NF-kappa B/NLRP3 inflammasome pathway HSPA8 inhibition protects spinal ischemia-reperfusion injury[J]. JOURNAL OF NEUROINFLAMMATION,2021,18(1).

Mi, Jingyi.,Yang, Yang.,Yao, Hao.,Huan, Zhirong.,Xu, Ce.,...&Ge, Xin.(2021).Inhibition of heat shock protein family A member 8 attenuates spinal cord ischemia-reperfusion injury via astrocyte NF-kappa B/NLRP3 inflammasome pathway HSPA8 inhibition protects spinal ischemia-reperfusion injury.JOURNAL OF NEUROINFLAMMATION,18(1).

Mi, Jingyi,et al."Inhibition of heat shock protein family A member 8 attenuates spinal cord ischemia-reperfusion injury via astrocyte NF-kappa B/NLRP3 inflammasome pathway HSPA8 inhibition protects spinal ischemia-reperfusion injury".JOURNAL OF NEUROINFLAMMATION 18.1(2021).