The Role Of STAT5 Regulated Autophagy In AGEs Induced Senescence Of Human Glomerular Mesangial Cells Which Can Be Regulated By Losartan

Introduction:Kidney has important physologycal functions,and appears the earlier one in humen aging.With the rapid progress and development in economy and society,China turns gradually to an aging society as a populous nation,though it is the elderly who are at high risk of chrnic kidney diseases(CKD).Kidney aging performs in histological(pathological)and cellular level.Series of complicated changes in structure,fuction,cellular fuction,molecular biology and epigenetics are in involved in the process of kidney aging.There is no generally acknowledged gold standard for cellular senescence,and less researches provide systematic studies in vivo and in vitro about the process of kidney aging.Glomerular mesangial cells(GMCs)are among the most impontant one in renal intrinsic cells,and maintain the metabolic balance of extracellular matrix in mesangial region.Changes in fuction and phnotype of CMCs play a crucial rule in the process of kidney aging.Autophagy is an highly conserved intracellular catabolic processes,which can be divided into macroautophagy,microautophagy and chaperone-mediated autophagy.Autophagy is a protective mechanism by which cells degrade their damaged or aged organelles and biological macromolecules through lysosomes to maintain the stability of intracellular environment.It plays an important role in the pathogenesis of human immunity,infection,inflammation,tumors,cardiovascular diseases.Hyperglycemia and Glycation End Products(AGEs)can lead to disfuctions in mammalian Target Of Rapamycin(mTOR)pathway,affecting the process of intracellular autophagy.Decreased autophagic activity may result in the inability of damaged organelles and aging-related modification proteins to be effectively cleared and aggregated within cells,leading to cellular senescence directly or indirectly.Our team has confirmed in pervious studies that high glucose/Ang II induces senescence of human glomerular mesangial cells(HGMC),and autophagy mediated by STAT3 signaling pathway plays an important role in this process.In 2018,our team further revealed that STAT3 pathway was activated in the process of natural aging-related glomerulosclerosis,accompanied by a significant decrease in autophagy,and confirmed the previous views in human kidney tissues in vivo for the first time.STAT5 belongs to the Signal Transducers and Activators of Transcription(STAT)as well STAT3,and has some overlap in upsteam with STAT3.In some studies,it is also found that STAT3 and STAT5may have synergistic relationship,but each has its own independence.Therefore,this study explored the role of STAT5 signaling pathway and autophagy in the aging process of human mesangial cells.Methods:Part 1:The final sample included 10 young subjects(...