.png){kind=icon}
.png){kind=icon}
Return
Mesenchymal Stem Cell-Derived Exosomal miR-29a-3p Improves Hypertrophic Scar by Inhibiting the Proliferation and Migration of Schwann Cells via the PDGFRB/PAK1 Axis
.png){kind=icon}
PRE
AI
C
R
F
L
C
S
R
Z
L
Y
DOI：10.1002/biof.70120.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
Mesenchymal stem cell-derived exosomes (MSC-exo) can alleviate hypertrophic scar (HS) formation, whereas Schwann cells (SCs) promote HS formation. This study aimed to investigate whether MSC-exos attenuate HS by modulating SCs and to elucidate the underlying mechanisms. HS and normal skin tissues were obtained from patients. MSCs, SCs, and fibroblasts were isolated from BALB/c mice. SCs and HS mouse models were treated with MSC-exos. SCs under various treatments were co-cultured with fibroblasts. mRNA and protein levels were assessed by qRT-PCR, western blot, immunofluorescence, and immunohistochemical staining. Cell migration, proliferation, and apoptosis were evaluated by wound healing assay, CCK-8 assay, and TUNEL assay, respectively. HS tissue morphology was examined by Hematoxylin–eosin and Masson staining. The targeting of miR-29a-3p towards PDGFRB was validated using a dual-luciferase reporter assay. In patient HS tissues, downregulated miR-29a-3p was negatively correlated with upregulated PDGFRB. MSC-exo-delivered miR-29a-3p suppressed SCs proliferation and migration, promoted SCs apoptosis, and reduced SCs-secreted NGF, thereby inhibiting fibroblast migration and myofibroblast transformation. These effects were reversed by miR-29a-3p knockdown in MSCs. Furthermore, miR-29a-3p targeted and inhibited PDGFRB expression in SCs. Silencing PDGFRB abolished the promoting effects of miR-29a-3p inhibition on SCs, which was rescued by the PAK1 activator FTY720. MSC-exo-delivered miR-29a-3p ameliorates HS by inhibiting SCs proliferation, migration and NGF secretion via the PDGFRB/PAK1 axis to suppress myofibroblast transformation. Beyond the traditional focus on fibroblasts, this reveals an exosome-SCs-fibroblast network, providing a novel theoretical basis for HS treatment.
Keywords:
hypertrophic scar
mesenchymal stem cell-derived exosome
miR-29a-3p
NGF
PDGFRB/PAK1 axis
Schwann cells
Journal
IF:
5
Papers:
2.2K
Citations:
5.9K
Organization
Cited Papers