TY - JOUR
T1 - Role of statins in regulating molecular pathways following traumatic brain injury
T2 - A system pharmacology study
AU - Mahmoudi, Ali
AU - Heydari, Sahar
AU - Markina, Yuliya V.
AU - Barreto, George E.
AU - Sahebkar, Amirhossein
N1 - Publisher Copyright:
© 2022 The Authors
PY - 2022/9
Y1 - 2022/9
N2 - Traumatic brain injury (TBI) is a serious disorder with debilitating physical and psychological complications. Previous studies have indicated that genetic factors have a critical role in modulating the secondary phase of injury in TBI. Statins have interesting pleiotropic properties such as antiapoptotic, antioxidative, and anti-inflammatory effects, which make them a suitable class of drugs for repurposing in TBI. In this study, we aimed to explore how statins modulate proteins and pathways involved in TBI using system pharmacology. We first explored the target associations with statins in two databases to discover critical clustering groups, candidate hub and critical hub genes in the network of TBI, and the possible connections of statins with TBI-related genes. Our results showed 1763 genes associated with TBI. Subsequently, the analysis of centralities in the PPI network displayed 55 candidate hub genes and 15 hub genes. Besides, MCODE analysis based on threshold score:10 determined four modular clusters. Intersection analysis of genes related to TBI and statins demonstrated 204 shared proteins, which suggested that statins influence 31 candidate hub and 9 hub genes. Moreover, statins had the highest interaction with MCODE1. The biological processes of the 31 shared proteins are related to gene expression, inflammation, antioxidant activity, and cell proliferation. Biological enriched pathways showed Programmed Cell Death proteins, AGE-RAGE signaling pathway, C-type lectin receptor signalling pathway, and MAPK signaling pathway as top clusters. In conclusion, statins could target several critical post-TBI genes mainly involved in inflammation and apoptosis, supporting the previous research results as a potential therapeutic agent.
AB - Traumatic brain injury (TBI) is a serious disorder with debilitating physical and psychological complications. Previous studies have indicated that genetic factors have a critical role in modulating the secondary phase of injury in TBI. Statins have interesting pleiotropic properties such as antiapoptotic, antioxidative, and anti-inflammatory effects, which make them a suitable class of drugs for repurposing in TBI. In this study, we aimed to explore how statins modulate proteins and pathways involved in TBI using system pharmacology. We first explored the target associations with statins in two databases to discover critical clustering groups, candidate hub and critical hub genes in the network of TBI, and the possible connections of statins with TBI-related genes. Our results showed 1763 genes associated with TBI. Subsequently, the analysis of centralities in the PPI network displayed 55 candidate hub genes and 15 hub genes. Besides, MCODE analysis based on threshold score:10 determined four modular clusters. Intersection analysis of genes related to TBI and statins demonstrated 204 shared proteins, which suggested that statins influence 31 candidate hub and 9 hub genes. Moreover, statins had the highest interaction with MCODE1. The biological processes of the 31 shared proteins are related to gene expression, inflammation, antioxidant activity, and cell proliferation. Biological enriched pathways showed Programmed Cell Death proteins, AGE-RAGE signaling pathway, C-type lectin receptor signalling pathway, and MAPK signaling pathway as top clusters. In conclusion, statins could target several critical post-TBI genes mainly involved in inflammation and apoptosis, supporting the previous research results as a potential therapeutic agent.
KW - Protein-protein interaction
KW - Statins
KW - Traumatic brain injury
UR - http://www.scopus.com/inward/record.url?scp=85132723800&partnerID=8YFLogxK
U2 - 10.1016/j.biopha.2022.113304
DO - 10.1016/j.biopha.2022.113304
M3 - Article
C2 - 35724514
AN - SCOPUS:85132723800
SN - 0753-3322
VL - 153
SP - 113304
JO - Biomedicine and Pharmacotherapy
JF - Biomedicine and Pharmacotherapy
M1 - 113304
ER -