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DNAJA1 KO on HUVECs with heat stress

ABSTRACT: HS-induced proteome changes in WT and DNAJA1-KO cells were quantified using label free-based quantitative proteomic analysis. Four groups:wild type HUVECs group, DNAJA1 knockout HUVECs group, WT HUVECs with heat stress group, DNAJA1 knockout HUVECs with heat stress group,were conducted label free-based quantitative proteomic analysis to detect the mechanism of DNAJA1's protective effects on heat stress.

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ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

SUBMITTER: Lei Li

LAB HEAD: Department of

PROVIDER: PXD043512 | Pride | 2024-03-26

REPOSITORIES: Pride

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Project description:Multiple sclerosis (MS) is a chronic, inflammatory, and demyelinating disease of the central nervous system (CNS). Ursolic acid (UA) can be used in the MS treatment with anti-inflammatory and neuroprotective activities. However, UA is insoluble in water, which may affect its medication effectiveness. In this study, we evaluated the pharmacological effects of UAOS-Na, a water-soluble UA derivative, on experimental autoimmune encephalomyelitis (EAE) mouse, explored its underlying mechanism, and verified the mechanism by in vitro and in vivo experiments. As we expected, UAOS-Na (30 mg/kg/d) delayed the onset time of EAE from 11.78 days post immunization (dpi) to 14.33 dpi, reduced the incidence from 90.0% to 42.9%, and was more effective than UA. UAOS-Na (60 mg/kg/d) significantly decreased the serum levels of IFN-γ, IL-17A, TNF-α and IL-6, reduced the mononuclear cell infiltration of spinal cord, and inhibited the overexpression of key transcription factors T-bet and ROR-γt of EAE mouse spinal cord and spleen. In addition, UAOS-Na attenuated demyelination and astrogliosis in the CNS of EAE and Cuprizone-induced mice. Mechanically, proteomics showed that 217 differential expression proteins (DEPs) were enriched and 215 were upregulated in EAE mice. After UAOS-Na treatment, 52 DEPs were enriched and 49 were downregulated, and these DEPs were markedly enriched in inositol phosphate metabolism, calcium, sphingolipid, cAMP, and antigen processing and presentation (APP) signaling pathways. Among them, there were few studies on APP signaling pathway related with MS. Therefore, we further investigated the effect of UAOS-Na on APP signaling pathway and found that UAOS-Na downregulated the protein levels of Tapbp and H2-T23 in MHC-I antigen presentation pathway and decreased the proliferation of splenic CD8 T cells, thereby inhibiting the CNS infiltration of CD8 T cells. Together, our findings demonstrated that UAOS-Na have both direct anti-demyelination and anti-inflammation effects. And it could reduce the inflammation of MS by downregulating the expression of Tapbp and H2-T23 in the MHC-I antigen presentation pathway.

			Action	DRS
	Ef22CJK_.pep.xml	Pepxml
	Ef22CJK_.prot.xml	Xml
	Ef22CJK_H1.raw	Raw
	Ef22CJK_H2.raw	Raw
	Ef22CJK_H3.raw	Raw

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DNAJA1 KO on HUVECs with heat stress

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