The Function Of Adamts18 On Renal Development And Dysfunctions

Kidney disease has become a global public health problem.It is closely related to various chronic diseases such as cardiovascular disease,diabetes mellitus and all-cause death.In recent years,the prevalence of chronic kidney disease(CKD)is increasing,which is up to 10.8%in China.Progress of CKD will induce renal failure and serious complications,resulting in high morbidity,high mortality and high medical costs.However,the effect of current treatment on kidney disease is limited and there are many problems remain to be solved.Thus,the early diagnosis and treatment of kidney disease poses an enormous challenge for public health.Inflammation is one of the main factors of CKD.Several ADAMTSs have been demonstrated as important inflammatory mediators.The expression profile has initially shown that Adamts18 is highly expressed in embryonic kidney but whose functions in renal development and injury remains unclear.We have previously,generated Adamtsl8 knockout(KO)mice.In this study,we utilized this genetically engineered Adamts18 KO mouse to shed light on the role of Adamts18 in renal development and injury.1.In the physiological state,we compared the renal development between wild type(WT)mice and Adamtsl8 KO mice.2.In lipopolysaccharide(LPS)-induced acute organ injury,we compared renal pathological changes between WT mice and Adamtsl8 KO mice.Experimental results:1.In the physiological state,42%of the Adamts18 KO mice at age of 3 weeks showed renal cortical atrophy and thinner renal cortex capillary basement membrane.We also found proliferation of mesangial matrix and mesangial cells by electron microscopy.2.In LPS-induced acute organ injury,the Adamtsl8 KO mice suffered more severe renal injuries,include in capillary bleeding,inflammatory infiltration,and even tubular urinary nitrogen retention compared to the WT mice.Conclusion:Adamtsl8 KO mice showed abnormal renal structure in physiological status and more severe injury in pathological status.To our knowledge,this is the first study of recognizing of the novel function of Adamtsl8 in the regulation of renal development and injury.Further study will be focused on the mechanism of how Adamtsl8 exert its effect on kidney which may provide new insights in the prevention and treatment of renal disease.