2. Academic Validation
  3. Transcriptomics changes of calcitonin gene-related peptide in mitigating lipopolysaccharide-induced septic cardiomyopathy

Transcriptomics changes of calcitonin gene-related peptide in mitigating lipopolysaccharide-induced septic cardiomyopathy

  • Sci Rep. 2024 Nov 2;14(1):26385. doi: 10.1038/s41598-024-77520-5.
Kexin Cai 1 2,  Siming Lin 1 2,  Gufeng Gao 2 3,  Mohammad Lsmail Hajary Sagor 2 3,  Yuqing Luo 1,  Zhihua Chen 1,  Jing Wang 1,  Mengjing Yang 1,  Guili Lian 4 5,  Zhihong Lin 6 7 8,  Shaodan Feng 9 10 11
Affiliations

Affiliations

  • 1 Department of Emergency, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China.
  • 2 Fujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China.
  • 3 Clinical Research Center for Geriatric Hypertension Disease of Fujian Province, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China.
  • 4 Fujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China. 59192286@qq.com.
  • 5 Clinical Research Center for Geriatric Hypertension Disease of Fujian Province, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China. 59192286@qq.com.
  • 6 Department of Emergency, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China. fzlinzh@163.com.
  • 7 Fujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China. fzlinzh@163.com.
  • 8 Department of Emergency, Binhai Campus of the First Affiliated Hospital, National Regional Medical Center, Fujian Medical University, Fuzhou, 350212, Fujian, China. fzlinzh@163.com.
  • 9 Department of Emergency, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China. sdfeng@fjmu.edu.cn.
  • 10 Fujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China. sdfeng@fjmu.edu.cn.
  • 11 Department of Emergency, Binhai Campus of the First Affiliated Hospital, National Regional Medical Center, Fujian Medical University, Fuzhou, 350212, Fujian, China. sdfeng@fjmu.edu.cn.
PMID: 39487252 DOI: 10.1038/s41598-024-77520-5
Abstract

Septic cardiomyopathy (SCM), a complication initiated by sepsis, presents a significant clinical challenge, leading to increased mortality rates. However, the mechanisms of SCM have not been fully uncovered. Our study involved analyzing RNA Sequencing (RNA-seq) data from rat heart tissue, along with utilizing molecular docking and molecular dynamics (MD) simulations, to discover key targets and potential pharmacological actions of the Calcitonin gene-related peptide (CGRP) against SCM. A lipopolysaccharide-induced SCM model was established in rats (LPS 10 mg/kg, intraperitoneal (i.p.)). Thereafter, the myocardial tissues from the three groups of rats (Ctrl group, LPS group, and CGRP group) (n = 5) were extracted and underwent RNA-seq, followed by bioinformatics analyses. The qPCR-validated hub targets potentially interacting with CGRP were identified. Following this, homology modeling was utilized to obtain the 3D structure of hub targets, and molecular docking was conducted to evaluate the interaction between CGRP and hub targets. MD simulations (300 ns) were performed to confirm the findings further. Our findings demonstrated that CGRP significantly lowered mortality in SCM rats. 633 DEGs were affected by LPS, contrasted with the Ctrl group. 96 DEGs were affected by CGRP compared to the LPS group. In total, ten fully annotated CGRP-triggered hub genes were obtained. The molecular docking and MD simulations indicate that the relationship between CGRP and eight hub genes is extremely strong. This research offers a thorough examination of the possible objectives and fundamental molecular processes of CGRP in combating SCM, laying the groundwork for investigating the potential protective mechanisms of CGRP against SCM.

Keywords

Bioinformatics; Calcitonin gene-related peptide; Molecular docking; Molecular dynamics; RNA-sequencing; Septic cardiomyopathy.

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