Haibo Li1, Renyi Kong2, Bowen Wan2, Lei Yang3, Sheng Zhang2, Xiaojian Cao4, Hongtao Chen5. 1. Department of Orthopedics, Affiliated Changzhou NO.2 People's Hospital of Nanjing Medical University, Changzhou, China. 2. Department of Orthopedics, First Affiliated Hospital of Nanjing Medical University, Nanjing, China. 3. Department of Orthopedics, Nanjing First Hospital, Nanjing, China. 4. Department of Orthopedics, First Affiliated Hospital of Nanjing Medical University, Nanjing, China. Electronic address: dr_cxj001@163.com. 5. Department of Orthopedics, First Affiliated Hospital of Nanjing Medical University, Nanjing, China. Electronic address: chtspine@163.com.
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.
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: Katarina Kiss Bimbova; Maria Bacova; Alexandra Kisucka; Jan Galik; Peter Zavacky; Nadezda Lukacova Journal: Mol Neurobiol Date: 2021-11-22 Impact factor: 5.590