Initiation of PI3K/AKT pathway by IGF-1 decreases spinal cord injury-induced endothelial apoptosis and microvascular damage.

Abstract

AIM:

Apoptosis of endothelial cells (ECs) is a crucial factor in blood-spinal cord barrier (BSCB) disruption post spinal cord injury (SCI). Insulin-like growth factor-1 (IGF-1) is a protective cytokine that plays an important role in multiple diseases, whereas the distinct role in SCI-induced remains critical questions to address. Here we designed to explore the role and underlying mechanism of IGF-1 in endothelial damage after SCI.

MAIN METHODS:

In the current study, we established mouse microvascular endothelial cells (MVECs) injury model via LPS and cDNA of IGF-1 was transfected into MVECs. In vivo SCI mice, overexpression of IGF-1 (SCI-IGF-1) and its corresponding empty vehicle (SCI-NC) were conducted using lentivirus, then apoptosis degree, component of tight junction, and inflammatory damage were evaluated.

KEY FINDINGS:

IGF-1 treatment in MVECs displayed a milder apoptosis and cell damage under LPS insult. IGF-1 increased the level of PI3K/AKT pathway, which impeded the procedure of apoptosis. Blocking of PI3K/AKT pathway markedly neutralized the effect of IGF-1 treatment. Transfection of excess IGF-1 into SCI mice significantly corrected microenvironment of neural tissue repair, reduced area of injured core and improved functional recovery with greater activation of PI3K/AKT pathway.

SIGNIFICANCE:

The results above argue that the promising roles played by IGF-1 is potentially vital for developing effective future therapies in SCI.

• Authors: Haibo Li, Renyi Kong, Bowen Wan, Lei Yang, Sheng Zhang, Xiaojian Cao, Hongtao Chen
• Journal: Life sciences (Life Sci) Vol. 263 Pg. 118572 (Dec 15 2020) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 33065147 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• insulin-like growth factor-1, mouse
• Insulin-Like Growth Factor I
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Apoptosis (physiology)
• Endothelial Cells (pathology)
• Insulin-Like Growth Factor I (genetics)
• Male
• Mice
• Mice, Inbred C57BL
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Recovery of Function (physiology)
• Spinal Cord Injuries (physiopathology, therapy)
• Tight Junctions (metabolism)
• Transfection