Bioinformatics on Screening and Pathway Analysis of Early Diabetic Nephropathy Related Genes

Authors

  • Yao Sang

DOI:

https://doi.org/10.62051/s0fd6k65

Keywords:

DN; gene screening; pathogenesis; bioinformatics; signaling pathways; DEGs.

Abstract

Diabetic nephropathy (DN), a severe complication arising from diabetes, necessitates timely diagnosis and therapeutic intervention to mitigate the disease’s progression. The objective of this article is to identify pivotal genes linked to the early stages of DN through the application of bioinformatics techniques. Furthermore, this this article endeavors to elucidate the signaling pathways associated with these genes, thereby offering novel therapeutic targets for the preemptive identification and management of DN. Methods: this article obtained the relevant gene chip data from the public dataset Gene Expression Omnibus (GEO) database, and obtained the information derived from the analysis of the complete set of genes being expressed of kidney tissue of DN patients and healthy controls. The R programming language, in conjunction with the Bioconductor package, was employed to perform an analysis of gene expression variations, with the aim of identifying obvious differential expressed genes (DEGs). Functional annotation and enrichment analysis: Functional categorization and enrichment of DEGs were conducted utilizing the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) resources, offering a deeper understanding of the molecular functions and pathways related to these genes. Protein-protein interaction (PPI) network construction: PPI networks of DEGs were constructed adopting search tool for the retrieval of interacting genes (STRING) database, and network visualization and key gene screening were performed by Cytoscape software. Other independent gene expression datasets and literature reports were used to verify the selected key genes. The results suggested that GSE176230 dataset was retrieved and downloaded from CEO database. After screening, there were 1,715 DEGs in DN and control samples, of which 1,026 were up-regulated and 689 were down-regulated. DEGs markedly associated with early DN (PBMCs, CXCL8, MMP9, 1L1B, C-C chemokine receptor type 2 (CCR2), TLR10, CX3CR1, P2RY14, APAF1, GREM1, FAM30A, PRKY, TMSB4Y, GDF3) were screened out. GO analysis indicated that a visible enrichment of these genes was observed in key biological processes, including inflammatory response, oxidative stress, apoptosis. KEGG pathway analysis suggested that the main signaling pathways involved included TGF-β, MAPK, and PI3K-Akt. PPI network analysis identified multiple key genes (CXCL8, MMP9, and CCR2). The mRNA levels of CXCL8, MMP9, and CCR2 in patients with early DN were markedly higher as against normal healthy people (P < 0.05). Utilizing bioinformatics techniques, this article effectively identified pivotal genes and associated signaling pathways that are linked to the early stages of DN. The insights gained from this article offer novel therapeutic targets and a foundational framework for the preemptive identification and management of DN. Upcoming research endeavors are poised to confirm the particular roles and mechanisms of these genetic elements and molecular pathwaysy.

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References

[1] von Morze C, Reed GD, Wang ZJ, Ohliger MA, Laustsen C. Hyperpolarized Carbon (13C) MRI of the Kidneys: Basic Concept. Methods Mol Biol 2021; 2216: 267-278.

[2] Greenwood SA, Koufaki P, Macdonald JH, Bulley C, Bhandari S, Burton JO, Dasgupta I, Farrington K, Ford I, Kalra PA, Kumwenda M, Macdougall IC, Messow CM, Mitra S, Reid C, Smith AC, Taal MW, Thomson PC, Wheeler DC, White C, Yaqoob M, Mercer TH. Exercise programme to improve quality of life for patients with end-stage kidney disease receiving haemodialysis: the PEDAL RCT. Health Technol Assess 2021; 25(40): 1-52.

[3] Müller A, Meier M. Assessment of Renal Volume with MRI: Experimental Protocol. Methods Mol Biol 2021; 2216: 369-382.

[4] von Morze C, Reed GD, Wang ZJ, Ohliger MA, Laustsen C. Hyperpolarized Carbon (13C) MRI of the Kidneys: Basic Concept. Methods Mol Biol 2021; 2216: 267-278.

[5] Jones J, Cain S, Pesic-Smith J, Choong PFM, Morokoff AP, Drummond KJ, Dabscheck G. Circulating tumor DNA for malignant peripheral nerve sheath tumors in neurofibromatosis type 1. J Neurooncol 2021; 154(3): 265-274.

[6] Williams KB, Largaespada DA. New Model Systems and the Development of Targeted Therapies for the Treatment of Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors. Genes (Basel) 2020; 11(5): 477.

[7] Hirbe AC, Kaushal M, Sharma MK, Dahiya S, Pekmezci M, Perry A, Gutmann DH. Clinical genomic profiling identifies TYK2 mutation and overexpression in patients with neurofibromatosis type 1-associated malignant peripheral nerve sheath tumors. Cancer 2017; 123(7): 1194-1201.

[8] Watson KL, Al Sannaa GA, Kivlin CM, Ingram DR, Landers SM, Roland CL, Cormier JN, Hunt KK, Feig BW, Ashleigh Guadagnolo B, Bishop AJ, Wang WL, Slopis JM, McCutcheon IE, Lazar AJ, Torres KE. Patterns of recurrence and survival in sporadic, neurofibromatosis Type 1-associated, and radiation-associated malignant peripheral nerve sheath tumors. J Neurosurg 2017; 126(1): 319-329.

[9] Park GH, Lee SJ, Yim H, Han JH, Kim HJ, Sohn YB, Ko JM, Jeong SY. TAGLN expression is upregulated in NF1-associated malignant peripheral nerve sheath tumors by hypomethylation in its promoter and subpromoter regions. Oncol Rep 2014; 32(4): 1347-54.

[10] Park GH, Lee SJ, Lee CG, Kim J, Park E, Jeong SY. Neurofibromin Deficiency Causes Epidermal Growth Factor Receptor Upregulation through the Activation of Ras/ERK/SP1 Signaling Pathway in Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheet Tumor. Int J Mol Sci 2021; 22(24): 13308.

[11] Kim A, Pratilas CA. The promise of signal transduction in genetically driven sarcomas of the nerve. Exp Neurol 2018; 299(Pt B): 317-325.

[12] Stein KK, Golden A. The C. elegans eggshell. WormBook 2018; 2018: 1-36.

[13] Jones-Hughes T, Snowsill T, Haasova M, Coelho H, Crathorne L, Cooper C, Mujica-Mota R, Peters J, Varley-Campbell J, Huxley N, Moore J, Allwood M, Lowe J, Hyde C, Hoyle M, Bond M, Anderson R. Immunosuppressive therapy for kidney transplantation in adults: a systematic review and economic model. Health Technol Assess 2016; 20(62): 1-594.

[14] Haasova M, Snowsill T, Jones-Hughes T, Crathorne L, Cooper C, Varley-Campbell J, Mujica-Mota R, Coelho H, Huxley N, Lowe J, Dudley J, Marks S, Hyde C, Bond M, Anderson R. Immunosuppressive therapy for kidney transplantation in children and adolescents: systematic review and economic evaluation. Health Technol Assess 2016; 20(61): 1-324.

[15] Simmons RK, Borch-Johnsen K, Lauritzen T, Rutten GE, Sandbæk A, van den Donk M, Black JA, Tao L, Wilson EC, Davies MJ, Khunti K, Sharp SJ, Wareham NJ, Griffin SJ. A randomised trial of the effect and cost-effectiveness of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with screen-detected type 2 diabetes: the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION-Europe) study. Health Technol Assess 2016; 20(64): 1-86.

[16] Griffin SJ, Rutten GEHM, Khunti K, Witte DR, Lauritzen T, Sharp SJ, Dalsgaard EM, Davies MJ, Irving GJ, Vos RC, Webb DR, Wareham NJ, Sandbæk A. Long-term effects of intensive multifactorial therapy in individuals with screen-detected type 2 diabetes in primary care: 10-year follow-up of the ADDITION-Europe cluster-randomised trial. Lancet Diabetes Endocrinol 2019; 7(12): 925-937.

[17] Griffin SJ, Borch-Johnsen K, Davies MJ, Khunti K, Rutten GE, Sandbæk A, Sharp SJ, Simmons RK, van den Donk M, Wareham NJ, Lauritzen T. Effect of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with type 2 diabetes detected by screening (ADDITION-Europe): a cluster-randomised trial. Lancet 2011; 378(9786): 156-67.

[18] Zhu S, Liu M, Bennett S, Wang Z, Pfleger KDG, Xu J. The molecular structure and role of CCL2 (MCP-1) and C-C chemokine receptor CCR2 in skeletal biology and diseases. J Cell Physiol 2021; 236(10): 7211-7222.

[19] Knowles CH, Booth L, Brown SR, Cross S, Eldridge S, Emmett C, Grossi U, Jordan M, Lacy-Colson J, Mason J, McLaughlin J, Moss-Morris R, Norton C, Scott SM, Stevens N, Taheri S, Yiannakou Y. Non-drug therapies for the management of chronic constipation in adults: the CapaCiTY research programme including three RCTs. Southampton (UK): NIHR Journals Library; 2021.

[20] Huma ZE, Sanchez J, Lim HD, Bridgford JL, Huang C, Parker BJ, Pazhamalil JG, Porebski BT, Pfleger KDG, Lane JR, Canals M, Stone MJ. Key determinants of selective binding and activation by the monocyte chemoattractant proteins at the chemokine receptor CCR2. Sci Signal 2017; 10(480): eaai8529.

[21] Du Q, Fu YX, Shu AM, Lv X, Chen YP, Gao YY, Chen J, Wang W, Lv GH, Lu JF, Xu HQ. Loganin alleviates macrophage infiltration and activation by inhibiting the MCP-1/CCR2 axis in diabetic nephropathy. Life Sci 2021; 272: 118808.

[22] He S, Yao L, Li J. Role of MCP-1/CCR2 axis in renal fibrosis: Mechanisms and therapeutic targeting. Medicine (Baltimore) 2023; 102(42): e35613.

[23] Liu SY, Chen J, Li YF. Clinical significance of serum interleukin-8 and soluble tumor necrosis factor-like weak inducer of apoptosis levels in patients with diabetic nephropathy. J Diabetes Investig 2018 Sep; 9(5): 1182-1188.

[24] Tang G, Li S, Zhang C, Chen H, Wang N, Feng Y. Clinical efficacies, underlying mechanisms and molecular targets of Chinese medicines for diabetic nephropathy treatment and management. Acta Pharm Sin B 2021; 11(9): 2749-2767.

[25] Li X, Zhang L, Yan C, Zeng H, Chen G, Qiu J. Relationship between immune cells and diabetic nephropathy: a Mendelian randomization study. Acta Diabetol 2024.

[26] Moser B, Loetscher P. Lymphocyte traffic control by chemokines [J]. Nat Immunol, 2001, 2(2): 123-128.

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Published

10-10-2024

How to Cite

Sang, Y. (2024). Bioinformatics on Screening and Pathway Analysis of Early Diabetic Nephropathy Related Genes. Transactions on Materials, Biotechnology and Life Sciences, 5, 109-117. https://doi.org/10.62051/s0fd6k65