Biomaterial Database

Exosomes derived from human umbilical cord mesenchymal stem cells (HUCMSC-EXO) regulate autophagy through AMPK-ULK1 signaling pathway to ameliorate diabetic cardiomyopathy. 2022

Zhiqiang Zhang, and Lei Chen, and Xueheng Chen, and Yiran Qin, and Chao Tian, and Xuening Dai, and Runqi Meng, and Yuanyuan Zhong, and Wenyan Liang, and Cheng Shen, and Jinguo Zhang, and Bin Zhang, and Xiqing Wei

Affiliated Hospital of Jining Medical University, Clinical Medical College, Jining Medical University, Jining, Shandong, 272000, China; Jining Key Laboratory for Diagnosis and Treatment of Cardiovascular Diseases, Jining, Shandong, 272000, China.

One of the main causes of severe diabetic heart failure and mortality is diabetic cardiomyopathy (DCM), a cardiovascular condition attributable to diabetes with a high incidence, a complicated and unexplained pathophysiology, and poor treatment results. Current findings have demonstrated that the onset of diabetic cardiomyopathy involves autophagy, inflammation, and mitochondrial damage. Myocardial autophagy behaves differently in different states,and one of the targets for the detection and treatment of cardiovascular illnesses like diabetic cardiomyopathy may be the control of autophagy. The role of human umbilical cord Mesenchymal stem cells-derived exosomes (HUCMSC-EXO) as a non-cellular system in the repair of cardiomyocytes, the evolution of diabetic cardiomyopathy and their cardioprotective effects are gradually being recognized. This study's objectives were to assess the therapeutic benefits of HUCMSC-EXO for diabetic cardiomyopathy and to look into their potential mechanisms of action. High-speed centrifugation was used to extract HUCMSC-EXO, and the shape of the exosomes was examined using transmission electron microscopy. Immunoblotting was used to determine the expression of CD9, CD63, and TSG101 molecules on the surface of the exosomes. A high-fat, high-sugar diet mixed with streptozotocin was used to build a rat model of type 2 diabetic cardiomyopathy. Cardiac function, ventricular wall thickness and cardiac histological changes were examined by cardiac ultrasound, serum BNP and histology. In cardiac myocytes, HUCMSC-EXO reduced the levels of autophagy-related protein expression. Additionally, immunoblotting supported our suspicion that this mechanism is strongly tied to the activation of the AMPK-ULK1 signaling pathway. So, we propose that it would be a good strategy to follow for treating diabetic cardiomyopathy. These findings offer both fresh concepts for building a model of diabetic cardiomyopathy and a creative theoretical framework for using HUCMSC-EXO to treat diabetic cardiomyopathy in a clinical setting.

UI	MeSH Term	Description	Entries
D003920	Diabetes Mellitus	A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071183	Autophagy-Related Proteins	Proteins and enzymes that function, often as components of MULTIPROTEIN COMPLEXES, to assemble AUTOPHAGOSOMES and carry out AUTOPHAGY.	Autophagy-Related Protein,Autophagy Related Protein,Autophagy Related Proteins,Protein, Autophagy-Related
D000071189	Autophagy-Related Protein-1 Homolog	A serine/threonine-protein kinase that functions in AUTOPHAGY in response to starvation. It acts on the PHOSPHATIDYLINOSITOL 3-KINASE complex PIK3C3 to regulate AUTOPHAGOSOME formation. It also functions as both a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) and is activated by AMPK, which it also negatively regulates.	Serine-Threonine Protein Kinase ULK1,ULK1 Protein,Unc-51 Like Autophagy Activating Kinase 1,Unc-51-Like Kinase 1,Autophagy Related Protein 1 Homolog,Serine Threonine Protein Kinase ULK1,Unc 51 Like Autophagy Activating Kinase 1,Unc 51 Like Kinase 1
D000073893	Sugars	Short chain carbohydrate molecules that have hydroxyl groups attached to each carbon atom unit with the exception of one carbon that has a doubly-bond aldehyde or ketone oxygen. Cyclical sugar molecules are formed when the aldehyde or ketone groups respectively form a hemiacetal or hemiketal bond with one of the hydroxyl carbons. The three dimensional structure of the sugar molecule occurs in a vast array of biological and synthetic classes of specialized compounds including AMINO SUGARS; CARBASUGARS; DEOXY SUGARS; SUGAR ACIDS; SUGAR ALCOHOLS; and SUGAR PHOSPHATES.	Sugar
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001343	Autophagy	The segregation and degradation of various cytoplasmic constituents via engulfment by MULTIVESICULAR BODIES; VACUOLES; or AUTOPHAGOSOMES and their digestion by LYSOSOMES. It plays an important role in BIOLOGICAL METAMORPHOSIS and in the removal of bone by OSTEOCLASTS. Defective autophagy is associated with various diseases, including NEURODEGENERATIVE DISEASES and cancer.	Autophagocytosis,ER-Phagy,Lipophagy,Nucleophagy,Reticulophagy,Ribophagy,Autophagy, Cellular,Cellular Autophagy,ER Phagy
D013311	Streptozocin	An antibiotic that is produced by Stretomyces achromogenes. It is used as an antineoplastic agent and to induce diabetes in experimental animals.	Streptozotocin,2-Deoxy-2-((methylnitrosoamino)carbonyl)amino-D-glucose,Streptozotocine,Zanosar
D014470	Umbilical Cord	The flexible rope-like structure that connects a developing FETUS to the PLACENTA in mammals. The cord contains blood vessels which carry oxygen and nutrients from the mother to the fetus and waste products away from the fetus.	Cord, Umbilical,Cords, Umbilical,Umbilical Cords
D015398	Signal Transduction	The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.	Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal