1. Initiation of PI3K/AKT pathway by IGF-1 decreases spinal cord injury-induced endothelial apoptosis and microvascular damage.
- Author
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Li H, Kong R, Wan B, Yang L, Zhang S, Cao X, and Chen H
- Subjects
- Animals, Male, Mice, Mice, Inbred C57BL, Phosphatidylinositol 3-Kinases metabolism, Proto-Oncogene Proteins c-akt metabolism, Recovery of Function physiology, Spinal Cord Injuries physiopathology, Tight Junctions metabolism, Transfection, Apoptosis physiology, Endothelial Cells pathology, Insulin-Like Growth Factor I genetics, Spinal Cord Injuries therapy
- 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., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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