Transcriptome Meta-Analysis Deciphers a Dysregulation in Immune Response-Associated Gene Signatures during Sepsis

Ahmad, Shaniya; Singh, Prithvi; Sharma, Archana; Arora, Shweta; Shriwash, Nitesh; Rahmani, Arshad Husain; Almatroodi, Saleh A.; Manda, Kailash; Dohare, Ravins; Syed, Mansoor Ali

doi:10.3390/genes10121005

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Transcriptome Meta-Analysis Deciphers a Dysregulation in Immune Response-Associated Gene Signatures during Sepsis

^1,†,

^2,†,

¹,

¹,

Arshad Husain Rahmani

⁴,

Saleh A. Almatroodi

⁴,

Kailash Manda

⁵,

Ravins Dohare

^2,*

and

Mansoor Ali Syed

^1,*

Translational Research Lab, Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi 110025, India

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, India

Department of Computer Science, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi 110025, India

⁴

Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraidah 51452, Saudi Arabia

⁵

Institute of Nuclear Medicine and Applied Sciences, Defence Research Development Organization, New Delhi 110054, India

Authors to whom correspondence should be addressed.

^†

Authors equally contributed.

Genes 2019, 10(12), 1005; https://doi.org/10.3390/genes10121005

Received: 19 October 2019 / Revised: 28 November 2019 / Accepted: 2 December 2019 / Published: 4 December 2019

(This article belongs to the Special Issue The Role of Genotoxicity in Infertility and Cancer Development)

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Abstract

Sepsis is a life-threatening disease induced by a systemic inflammatory response, which leads to organ dysfunction and mortality. In sepsis, the host immune response is depressed and unable to cope with infection; no drug is currently available to treat this. The lungs are frequently the starting point for sepsis. This study aimed to identify potential genes for diagnostics and therapeutic purposes in sepsis by a comprehensive bioinformatics analysis. Our criteria are to unravel sepsis-associated signature genes from gene expression datasets. Differentially expressed genes (DEGs) were identified from samples of sepsis patients using a meta-analysis and then further subjected to functional enrichment and protein‒protein interaction (PPI) network analysis for examining their potential functions. Finally, the expression of the topmost upregulated genes (ARG1, IL1R2, ELANE, MMP9) was quantified by reverse transcriptase-PCR (RT-PCR), and myeloperoxidase (MPO) expression was confirmed by immunohistochemistry (IHC) staining in the lungs of a well-established sepsis mouse model. We found that all the four genes were upregulated in semiquantitative RT-PCR studies; however, MMP9 showed a nonsignificant increase in expression. MPO staining showed strong immunoreactivity in sepsis as compared to the control. This study demonstrates the role of significant and widespread immune activation (IL1R2, MMP9), along with oxidative stress (ARG1) and the recruitment of neutrophils, in sepsis (ELANE, MPO). View Full-Text

Keywords: sepsis; meta-analysis; DEG; PPI

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Ahmad, S.; Singh, P.; Sharma, A.; Arora, S.; Shriwash, N.; Rahmani, A.H.; Almatroodi, S.A.; Manda, K.; Dohare, R.; Syed, M.A. Transcriptome Meta-Analysis Deciphers a Dysregulation in Immune Response-Associated Gene Signatures during Sepsis. Genes 2019, 10, 1005. https://doi.org/10.3390/genes10121005

AMA Style

Ahmad S, Singh P, Sharma A, Arora S, Shriwash N, Rahmani AH, Almatroodi SA, Manda K, Dohare R, Syed MA. Transcriptome Meta-Analysis Deciphers a Dysregulation in Immune Response-Associated Gene Signatures during Sepsis. Genes. 2019; 10(12):1005. https://doi.org/10.3390/genes10121005

Chicago/Turabian Style

Ahmad, Shaniya, Prithvi Singh, Archana Sharma, Shweta Arora, Nitesh Shriwash, Arshad H. Rahmani, Saleh A. Almatroodi, Kailash Manda, Ravins Dohare, and Mansoor A. Syed. 2019. "Transcriptome Meta-Analysis Deciphers a Dysregulation in Immune Response-Associated Gene Signatures during Sepsis" Genes 10, no. 12: 1005. https://doi.org/10.3390/genes10121005

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Transcriptome Meta-Analysis Deciphers a Dysregulation in Immune Response-Associated Gene Signatures during Sepsis

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