Liu Jing,Liu Mingxue,Yang Zhenyu,et al.Comparative proteomic analysis of congenital ureteropelvic junction stenosis[J].Journal of Clinical Pediatric Surgery,,21():474-481.[doi:10.3760/cma.j.cn101785-202104005-014]
Comparative proteomic analysis of congenital ureteropelvic junction stenosis
- Abstract:
- Objective To conduct comparative proteomics study between the stenotic and the normal u- reteral tissues adjacent to the stenotic ureter in children with ureteropelvic junction (UPJ) stenosis, and explore the etiology and pathogenesis of congenital UPJ stenosis. Methods 30 children with congenital UPJ stenosis underwent Anderson-Hynes operation. The ureteral tissue of the narrow segment (group A) and the normal ure- teral tissue adjacent to the distal end of the stenosis(group B) were taken immediately after the operation. A relative quantitative method of high-throughput proteomics based on tandem mass tag (TMT) was used to screen the differentially expressed proteins in these two groups. And then the targeted proteomics quantitative verification of the screened differential proteins was carried out by parallel reaction monitoring (PRM). Gene Ontology (GO) functional annotation, Kyoto Encyclopedia of genes and genomics (KEGG) pathway were en- riched and analyzed by bioinformatics method, and protein-protein interaction (PPI) network was analyzed. Results A total of 6093 proteins were identified in the two groups of specimens, including 160 differential pro- teins, of which 65 were up-regulated and 95 were down-regulated. Among the 9 target proteins subjected to PRM relative quantitative analysis, the ratio of protein content of 7 proteins including carbonic anhydrase 1 in group A and group B was less than 1 in the quantitative results of PRM and TMT;Glypican The ratio of protein content of -6 and RNA-binding proteins with multiple splicing in group A to group B was greater than 1 in the quantitative results of PRM and TMT. GO functional enrichment analysis found that the GO functional enrich- ment of differentially expressed proteins in the two groups in biological processes such as humoral immune re- sponse, anti-microbial humoral response, response to fungi, defense response to fungi, and defense response to bacteria were significantly higher. High level of significance(P < 0. 05). The results of KEGG pathway enrich- ment analysis showed that the enrichment of 20 signaling pathways including nitrogen metabolism and PPAR signaling pathway had a high significant level (P < 0. 05). In the PPI network, the most connected proteins were:neutrophil elastase (connectivity of 9) and cathepsin antimicrobial peptide (connectivity of 8). Conclusion The results of comparative proteomics suggest that the pathogenesis of congenital UPJ stenosis is related to microbial infection, which provides a reference for further study on the etiology and pathogenesis of this disease.
References:
[1] Liu M, Liu J, Liu X, et al. Peroxiredoxin I protein, a potential bio- marker of hydronephrosis in fetal mice exposure to 2,3,7,8-tet- rachlorodibenzo-p-dioxin[J]. J Pediatr Urol, 2014, 10(3):474-481. DOI:10. 1016/j. jpurol. 2013. 10. 005.
[2] 刘明学, 魏光辉, 刘靖, 等. 2,3,7,8-TCDD所致胎鼠肾积水发生机制的研究[J]. 中华小儿外科杂志, 2009, 30(4):253-256. DOI:10. 3760/cma. j. jssn. 0253-3006. 2009. 04. 020. Liu MX, Wei GH, Liu J, et al. 2, 3, 7, 8-TCDD induced hydro- nephrus is in murine fetuses[J]. Chin J Pediatr Surg, 2009, 30(4):253-256. DOI:10. 3760/cma. j. jssn. 0253-3006. 2009. 04. 020.
[3] Wi?niewski JR, Zougman A, Nagaraj N, et al. Universal sample preparation method for proteome analysis[J]. Nat Methods, 2009,6(5):359-362. DOI:10. 1038/nmeth. 1322.
[4] Dong W, Qiu C, Gong D, et al. Proteomics and bioinformatics ap- proaches for the identification of plasma biomarkers to detect Parkinson’s disease[J]. Exp Ther Med, 2019, 18(4):2833-2842. DOI:10. 3892/etm. 2019. 7888.
[5] Guo X, Liu C, Wang GB, et al. Quantitative proteomics and bioin- formatics analyses of human coronary artery endothelial cell inju- ry induced by Kawasaki disease[J]. Chinese Journal of Contem- porary Pediatrics,2020,22(7):796-803. DOI:10. 7499/j. issn. 1008-8830. 2001069.
[6] McAlister GC, Huttlin EL, Haas W, et al. Increasing the multiple- xing capacity of TMTs using reporter ion isotopologues with iso- baric masses[J]. Anal Chem,2012,84(17):7469-7478. DOI:10. 1021/ac301572t.
[7] Sopha P, Kadokura H, Yamamoto YH, et al. A novel mammalian ER-located J-protein, DNAJB14, can accelerate ERAD of mis- folded membrane proteins[J]. Cell Struct Funct, 2012, 37(2):177-187. DOI:10. 1247/csf. 12017.
[8] Gitlin AD, Heger K, Schubert AF, et al. Integration of innate im- mune signalling by caspase-8 cleavage of N4BP1[J]. Nature, 2020,587(7833):275-280. DOI:10. 1038/s41586-020-2796-5.
[9] Wu W, Jin YQ, Gao Z. Directly reprogramming fibroblasts into adipogenic, neurogenic and hepatogenic differentiation lineages by defined factors[J]. Exp Ther Med, 2017, 13(6):2685-2690. DOI:10. 3892/etm. 2017. 4365.
[10] Cassandri M, Smirnov A, Novelli F, et al. Zinc-finger proteins in health and disease[J]. Cell Death Discov,2017,3:17071. DOI:10. 1038/cddiscovery. 2017. 71. eCollection 2017.
[11] Gandotra S, Le Dour C, Bottomley W, et al. Perilipin deficiency and autosomal dominant partial lipodystrophy[J]. N Engl J Med, 2011,364(8):740-748. DOI:10. 1056/NEJMoa1007487.
[12] Mahajan S, Mellins ED, Faccio R. Diacylglycerol Kinase Regu- lates Macrophage Responses in Juvenile Arthritis and Cytokine Storm Syndrome Mouse Models[J]. J Immunol, 2020, 204(1):137-146. DOI:10. 4049/jimmunol. 1900721.
[13] Zhang S, Liu G, Xu C, et al. Perilipin 1 Mediates Lipid Metabo- lism Homeostasis and Inhibits Inflammatory Cytokine Synthesis in Bovine Adipocytes[J]. Front Immunol, 2018, 9:467. DOI:10. 3389/fimmu. 2018. 00467.
[14] Bals R, Wang X, Zasloff M, et al. The peptide antibiotic LL-37/hCAP-18 is expressed in epithelia of the human lung where it has broad antimicrobial activity at the airway surface[J]. Proc Natl Acad Sci U S A, 1998, 95(16):9541-9546. DOI:10. 1073/pnas. 95. 16. 9541.
[15] Bowdish DM, Davidson DJ, Lau YE, et al. Impact of LL-37 on an- ti-infective immunity[J]. J Leukoc Biol,2005,77(4):451-459. DOI:10. 1189/jlb. 0704380.
[16] Furuhashi M, Ishimura S, Ota H, et al. Lipid chaperones and met- abolic inflammation[J]. Int J Inflam, 2011:642612. DOI:10. 4061/2011/642612.
[17] Furuhashi M, Saitoh S, Shimamoto K, et al. Fatty Acid-Binding Protein 4(FABP4):Pathophysiological Insights and Potent Clini- cal Biomarker of Metabolic and Cardiovascular Diseases[J]. Clin Med Insights Cardiol,2015,8(Suppl 3):23-33. DOI:10. 4137/CMC. S17067.
[18] Hotamisligil GS, Bernlohr DA. Metabolic functions of FABPs- mechanisms and therapeutic implications[J]. Nat Rev Endocri- nol,2015,11(10):592-605. DOI:10. 1038/nrendo. 2015. 122.
[19] Li H, Huang X, Chang X, et al. S100-A9 protein in exosomes de- rived from follicular fluid promotes inflammation via activation of NF-κB pathway in polycystic ovary syndrome[J]. J Cell Mol Med,2020,24(1):114-125. DOI:10. 1111/jcmm. 14642.
[20] Pan T, Liu J, Xu S, et al. ANKRD22, a novel tumor microenviron- ment-induced mitochondrial protein promotes metabolic repro- gramming of colorectal cancer cells[J]. Theranostics, 2020, 10(2):516-536. DOI:10. 7150/thno. 37472.
[21] Singh BK, Kambayashi T. The Immunomodulatory Functions of Diacylglycerol Kinase[J]. Front Cell Dev Biol, 2016, 4:96. DOI:10. 3389/fcell. 2016. 00096.
[22] Chromek M, Slamová Z, Bergman P, et al. The antimicrobial pep- tide cathelicidin protects the urinary tract against invasive bacteri- al infection[J]. Nat Med, 2006, 12(6):636-641. DOI:10. 1038/nm1407.
[23] Peng H, Purkerson JM, Schwaderer AL, et al. Metabolic acidosis stimulates the production of the antimicrobial peptide cathelicidin in rabbit urine[J]. Am J Physiol Renal Physiol, 2017, 313(5):F1061-F1067. DOI:10. 1152/ajprenal. 00701. 2016.
[24] Ramanathan B, Davis EG, Ross CR, et al. Cathelicidins:microbi- cidal activity, mechanisms of action, and roles in innate immunity[J]. Microbes Infect, 2002, 4:361-372. DOI:10. 1016/s1286-4579(02) 01549-6.
[25] Di Francesco A, Favaroni A, Donati M. Host defense peptides:General overview and an update on their activity against Chlamydia spp[J]. Expert Rev Anti Infect Ther, 2013, 11(11):1215-1224. DOI:10. 1586/14787210. 2013. 841450.
[26] Buck CB, Day PM, Thompson CD, et al. Human alpha-defensins block papillomavirus infection[J]. Proc Natl Acad Sci USA, 2006,103(5):1516-1521. DOI:10. 1073/pnas. 0508033103.
[27] Kang J, Dietz MJ, Li B. Antimicrobial peptide LL-37 is bactericid- al against Staphylococcus aureus biofilms[J]. PLoS One, 2019, 14(6):e0216676. DOI:10. 1371/journal. pone. 0216676. eCol- lection 2019.
[28] Deshpande D, Grieshober M, Wondany F, et al. Super-Resolution Microscopy Reveals a Direct Interaction of Intracellular Mycobac- terium tuberculosis with the Antimicrobial Peptide LL-37[J]. Int J Mol Sci,2020,21(18):6741. DOI:10. 3390/ijms21186741.
[29] Kumar S, Gupta E, Kaushik S, et al. Neutrophil extracellular traps:formation and involvement in disease progression[J]. Iran J Allergy Asthma Immunol,2018,17(3):208-220.
[30] Thierry AR. Anti-protease Treatments targeting plasmin (ogen) and neutrophil elastase may be beneficial in fighting COVID-19[J]. Physiol Rev, 2020, 100(4):1597-1598. DOI:10. 1152/physrev. 00019. 2020.
[31] Zimmermann F, Lautenschl?ger K, Heppert V, et al. Expression of elastase on polymorphonuclear neutrophils in vitro and in vivo:i- dentification of CD11 b as ligand for the surface-bound elastase[J]. Shock,2005,23(3):216-223.
[32] Moideen K, Kumar NP, Nair D, et al. Heightened Systemic Levels of Neutrophil and Eosinophil Granular Proteins in Pulmonary Tu- berculosis and Reversal following Treatment[J]. Infect Immun, 2018,86(6):e00008-18. DOI:10. 1128/IAI. 00008-18. Print 2018 Jun.
[33] Chen Z, Shao X, Dou X, et al. Role of the Mycoplasma pneumoni- ae/Interleukin-8/Neutrophil Axis in the Pathogenesis of Pneumo- nia[J]. PLoS One,2016,11(1):e0146377. DOI:10. 1371/jour- nal. pone. 0146377. eCollection 2016.
Memo
收稿日期:2021-4-4。
基金项目:福建省自然科学基金（2019J01564）
通讯作者:刘明学,Email:983759194@qq.com