Tumor necrosis factor-stimulated gene-6 ameliorates early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome-mediated astrocyte pyroptosis

Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective treatment.Pyroptosis is a crucial mechanism underlying early brain injury after subarachnoid hemorrhage.Previous studies have confirmed that tumor necrosis factor-stimulated gene-6(TSG-6)can exert a neuroprotective effect by suppressing oxidative stress and apoptosis.However,no study to date has explored whether TSG-6 can alleviate pyroptosis in early brain injury after subarachnoid hemorrhage.In this study,a C57BL/6J mouse model of subarachnoid hemorrhage was established using the endovascular perforation method.Our results indicated that TSG-6 expression was predominantly detected in astrocytes,along with NLRC4 and gasdermin-D(GSDMD).The expression of NLRC4,GSDMD and its N-terminal domain(GSDMD-N),and cleaved caspase-1 was significantly enhanced after subarachnoid hemorrhage and accompanied by brain edema and neurological impairment.To explore how TSG-6 affects pyroptosis during early brain injury after subarachnoid hemorrhage,recombinant human TSG-6 or a siRNA targeting TSG-6 was injected into the cerebral ventricles.Exogenous TSG-6 administration downregulated the expression of NLRC4 and pyroptosis-associated proteins and alleviated brain edema and neurological deficits.Moreover,TSG-6 knockdown further increased the expression of NLRC4,which was accompanied by more severe astrocyte pyroptosis.In summary,our study revealed that TSG-6 provides neuroprotection against early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome activation-induced astrocyte pyroptosis.

Correlation of TSG-6 expression with apoptosis and collagen metabolism in pathological scar tissue

Objective: To study the correlation of tumor necrosis factor- stimulated gene-6 (TSG-6) expression with apoptosis and collagen metabolism in pathological scar tissue. Methods:Surgically removed pathological scar tissue and the normal skin tissue removed due to extremity trauma in Sichuan Provincial People's Hospital between June 2014 and February 2017 were selected to detect the mRNA expression of TSG-6 as well as the protein levels of apoptosis genes and collagen metabolism indexes. Results: TSG-6 mRNA expression as well as Smac, p53, Cyt-C, IGF-1 and bFGF protein levels in pathological scar tissue was significantly lower than those in normal skin tissue while Livin, PCNA, Col-I, Col-III and TGF-β1 protein levels were significantly higher than those in normal skin tissue;Livin, PCNA, Col-I, Col-III and TGF-β1 protein levels in pathological scar tissue with higher TSG-6 expression were lower than those in pathological scar tissue with lower TSG-6 expression while Smac, p53, Cyt-C, IGF-1 and bFGF protein levels were significantly higher than those in pathological scar tissue with lower TSG-6 expression. Conclusion: The low expression of TSG-6 in pathological scar tissue can inhibit apoptosis and promote collagen anabolism to accelerate scar formation.