Proteomics Study On Kidneys Of Mice Infected With Babesia Microti

Babesia is a type of blood parasitic protozoa transmitted by ticks.So far,more than 100 species have been found,many of which can cause zoonotic babesiosis.The Babesia microti involved in this study is one of the pathogens of human Babesia.Babesiasis is widely transmitted worldwide through ticks,which severely affects human health and economic development.Babesiasis occurs mainly in Zhejiang,Yunnan,and Inner Mongolia in China.The incubation period of Babesia microti disease is generally 1-3 weeks.Patients are accompanied by a series of symptoms such as headache,fever,nausea,and vomiting,and the kidneys,spleen and other tissues are easily damaged.In this study,histopathology was used to observe the kidney tissue of mice infected with Babesia.It was found that after BALB / C mice were infected with Babesia,kidney tissues were damaged,such as ischemia,abnormal renal function,and abnormal cell morphology.By observing the hematoxylin-eosin staining of the kidney,it was found that renal cells showed loose renal cell arrangement and renal vascular ischemia at the peak of infection,and renal cells gradually arranged tightly during recovery and basically returned to the pre-infection state.Then,we used DIA quantitative proteomics to study the total proteins and phosphorylated proteins of kidney tissues in the five stages of Babesia infection.Bioinformatics analysis was performed on proteins that differed in protein expression and degree of phosphorylation modification.Explore the role of these proteins in kidney damage and repair.Quantitative results of total protein in kidney tissues of mice before and after Babesia infection were as follows: 2473 proteins were identified in the uninfected group(0 d)and 5 d,8 d,11 d and 19 d after Babesia infection there were 1364 differentially changed proteins.Bioinformatics analysis of these differentially expressed proteins revealed that GO enrichment results show that differentially expressed proteins are mainly involved in molecular functions such as catalytic activity,binding process,and molecular regulation.Found during KEGG analysis,Peroxisome membrane protein,?-methyl-CoA racemase,fatty acyl-CoA oxidase,hydroxysteroid dehydrogenase 4,tris-acyl-CoA dehydrogenase,acetyl-CoA acyltransferase 1 plays a role in the oxidase pathway.These proteins combine to participate in the ?-oxidation of fatty acids in peroxisomes,and the expression of these proteins decreases after infection with Babesia microti,which results in abnormal fatty acid oxidation and lipid metabolism disorders.In addition,the expression of carbonic anhydrase 2,glutaminase,glutamate dehydrogenase,and phosphoenolpyruvate carboxykinase involved in bicarbonate recovery / regeneration of proximal tubules was down-regulated,resulting in a decrease in renal tubule recovery and regeneration capacity.It is easy to cause renal tubular acidosis,which indicates that infection with Babesia microti can cause kidney tissue damage.Based on the analysis of the results of kidney tissue phosphorylation protein identification,9503,9684,9087,9254,9464 phosphorylated peptides were identified in the five periods,and a total of 3668 cross-linked phosphorylated peptides were identified in the five periods.Among them,there were 3023 different phosphorylated peptides,corresponding to 1,229 phosphorylated proteins.Bioinformatics analysis of these differentially changed phosphorylated proteins found that these phosphorylated proteins are mainly involved in molecular functions such as the binding process,catalytic activity,and molecular regulation.It was found in KEGG pathway analysis that the levels of phosphorylation of serine / threonine protein kinases and transcriptional co-activators involved in the Hippo pathway were up-regulated at the peak of infection,inhibited target gene transcription,and promoted apoptosis.P21 activates kinase 4,and myosin light chain kinase participates in the regulation of myosin cytoskeleton,which increases the level of phosphorylation modification at the peak of infection,promotes cytoskeleton regulation,and resists the invasion of Babesia.The results provided a theoretical basis for clarifying the molecular mechanism of damage to the host kidney and the molecular mechanism of renal repair by Babesia microti,and also provided new ideas for the diagnosis and treatment of Babesia microti.