Role of the nuclear factor-kappa B signaling pathway in the repair of white matter injury in neonatal rats through human umbilical cord mesenchymal stem cell transplantation.
10.7499/j.issn.1008-8830.2408099
- Author:
Shu-Juan ZHANG
1
;
Chao WANG
1
;
Qian-Qian XU
1
;
Jun ZHANG
1
;
Yan-Ping ZHU
Author Information
1. Department of Neonatology, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China.
- Publication Type:Journal Article
- Keywords:
Human umbilical cord mesenchymal stem cell;
Neonatal rat;
Nuclear factor-kappa B pathway;
White matter injury
- MeSH:
Animals;
Rats, Sprague-Dawley;
White Matter/metabolism*;
Rats;
Signal Transduction;
Mesenchymal Stem Cell Transplantation;
Humans;
NF-kappa B/metabolism*;
Animals, Newborn;
Umbilical Cord/cytology*;
Male;
NF-KappaB Inhibitor alpha/metabolism*;
I-kappa B Proteins/genetics*;
Microfilament Proteins/analysis*;
Calcium-Binding Proteins/metabolism*;
Female
- From:
Chinese Journal of Contemporary Pediatrics
2024;26(12):1352-1361
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To observe the reparative effects of human umbilical cord mesenchymal stem cell (hUC-MSC) transplantation on white matter injury (WMI) in neonatal rats and explore its mechanism through the nuclear factor-kappa B (NF-κB) signaling pathway mediated by microglial cells.
METHODS:Sprague-Dawley rats, aged 2 days, were randomly divided into three groups: sham-operation,WMI, and hUC-MSC (n=18 each). Fourteen days after modeling, hematoxylin-eosin staining was used to observe pathological changes in the white matter, and immunofluorescence staining was used to measure the expression level of ionized calcium-binding adapter molecule 1 (Iba1). Western blotting was used to measure the protein expression levels of inhibitory subunit of nuclear factor-kappa B alpha (IκBα), phosphorylated IκBα (p-IκBα), phosphorylated NF-κB p65 (p-NF-κB p65), myelin basic protein (MBP), and neuron-specific nuclear protein (NeuN). Quantitative real-time PCR was used to assess the mRNA expression levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), MBP, and NeuN. Immunohistochemistry was used to measure the protein expression levels of MBP and NeuN. On day 28, the Morris water maze test was used to evaluate spatial cognitive ability.
RESULTS:Fourteen days after modeling, the sham-operation group exhibited intact white matter structure with normal cell morphology and orderly nerve fiber arrangement. In the WMI group, large-scale cell degeneration and necrosis were observed, and nerve fiber arrangement was disordered. The hUC-MSC group showed relatively normal cell morphology and more orderly nerve fibers. Compared with the sham-operation group, the WMI group had significantly higher proportions of Iba1-positive cells, increased protein levels of p-IκBα and p-NF-κB p65, and higher mRNA levels of TNF-α and IL-1β. The protein expression of IκBα and the positive expression of MBP and NeuN, as well as their protein and mRNA levels, were significantly reduced in the WMI group (P<0.05). Compared with the WMI group, the hUC-MSC group showed reduced proportions of Iba1-positive cells, decreased protein levels of p-IκBα and p-NF-κB p65, and lower mRNA levels of TNF-α and IL-1β. Furthermore, IκBα protein expression and MBP and NeuN expression (both at the protein and mRNA levels) were significantly increased in the hUC-MSC group (P<0.05). On day 28, the Morris water maze results showed that compared with the sham-operation group, the WMI group had significantly longer escape latency and fewer platform crossings (P<0.05). In contrast, the hUC-MSC group had significantly shorter escape latency and more platform crossings than the WMI group (P<0.05).
CONCLUSIONS:hUC-MSC transplantation can repair WMI in neonatal rats, promote the maturation of oligodendrocytes, and support neuronal survival, likely by inhibiting activation of the NF-κB signaling pathway mediated by microglial cells.
