Intracellular Domain Of CD44 Negatively Regulates Autophagy And Its Role In Vascular Endothelial Senescence

CD44 is a transmembrane protein widely distributed in cells,and its main function lies in the interaction between cells and cells,cells and matrices.CD44 promotes tumor cell invasion and metastasis.Autophagy is a biological process in which eukaryotic cells use lysosomes to degrade damaged organelles and misfolded proteins in cells.In this process,the double-layer membrane shed from the ribosome-free attachment zone of the rough endoplasmic reticulum wraps the desired degradation material to form autophagosomes,and then autophagosomes further combine with lysosomes to form autophagolysosomes for degradation.Previous studies in our laboratory found that CD44 knockout mice enhanced autophagy in aortic endothelial cells,and CD44 negatively regulated autophagy in vascular endothelial cells.Further studies found that CD44 mainly plays a role in autophagy regulation through the intracellular domain(CD44ICD).In this study,we constructed CD44ICD-specific vascular endothelial overexpression(Cd44icd-Tek-Cre-Egfp mice)mice.Two autophagy activators,rapamycin and trehalose,enhance the level of autophagy in mice,In this way,we can explore the role of CD44 ICD in regulating the autophagy and aging in the vascular of mouse.Make it is expected to become a new target for regulating autophagy and aging,and provide a new experimental basis for revealing the mechanism of autophagy-related vascular aging.Furthermore,we identified the curcumin analog(3E,5E)-1-methyl-3-(4-hydroxybenzylidene)-5-(3-indolomethylene)-piperidin-4-one(CUR5g)is a new autophagy inhibitor that affects the autophagy of different types of cancer cells,but it has no significant effect on normal cell autophagy.CUR5 g inhibits autophagy by blocking the fusion of autophagosomes and lysosomes.CUR5 g can significantly improve the efficacy of the chemotherapeutic drug cisplatin against non-small cell lung cancer.Our study provides a new tool for selectively inhibiting autophagy in lung cancer cells and a potential drug candidate for combination therapy in non-small cell lung cancer.