1.Advances in Toll-like Receptor Signaling Pathway Induced by Pyrogens
Mingren WANG ; Can WANG ; Gang CHEN
China Pharmacist 2018;21(3):480-484
Lipopolysaccharide(LPS),lipteichoic acid(LTA) and zymosan can be recognized by Toll-like receptors (TLRs) ex-pressing in the inflammatory cells membrane,such as macrophages,monocytes and endothelial cells,and then induce the secretion of pyrogenic cytokines followed by triggering inflammatory reaction. The signaling pathway mechanisms were summarized, including the extracellular signaling cascades from pyrogens to individual TLRs,and intracellular signaling cascades from TLRs to nucleus.
2.SARS-CoV-2 induces cardiomyocyte apoptosis by targeting the CypA/CD147 receptor pathway
Mingren MA ; Ling MA ; Yan LIU ; Fei WANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(5):734-740
【Objective】 To explore the possible mechanism of apoptosis induced by SARS-CoV-2 targeting cyclophilin A (CypA)/CD147 receptor pathway. 【Methods】 The pEncmv-SARS-CoV-2 S-3xflag recombinant plasmid was constructed and transfected into H9C2 cells. Apoptosis was analyzed by TUNEL assay, flow cytometry and DNA ladder. The interaction between CD147 and SARS-CoV-2 S protein was verified by CoIP. The expressions of apoptosis-related proteins were detected by Western blotting. 【Results】 Compared with the control group, TUNEL assay and flow cytometry showed that apoptosis was significantly increased in transfection group (P<0.05), and DNA ladder analysis showed that DNA degradation was obvious. The expression levels of Caspase12 and DR3 were significantly increased (P<0.001), the expression level of FAS was slightly increased (P<0.01), while the expression levels of TRF1 and DR4 were decreased (P<0.01). 【Conclusion】 SARS-CoV-2 S protein targets CypA/CD147 receptor to invade host cells, activate endoplasmic network pathway (Caspase12) and death receptor pathway (DR3, FAS), and induce apoptosis of cardiomyocytes through endogenous and exogenous apoptotic pathways.