Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0038454 (
stroke
)
147,016
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Forkhead box protein C1
(
FOXC1
) is known to regulate developmental processes in the skull and brain.
Methods
: The unique multipotent arachnoid-pia stem cells (APSCs) isolated from human and mouse arachnoid-pia membranes of meninges were grown as 3D spheres and displayed a capacity for self-renewal. Additionally, APSCs also expressed the surface antigens as mesenchymal stem cells. By applying the
FOXC1
knockout mice and mouse brain explants, signaling cascade of
FOXC1
-STI-1-PrP
C
was investigated to demonstrate the molecular regulatory pathway for APSCs self-renewal. Moreover, APSCs implantation in
stroke
model was also verified whether neurogenic property of APSCs could repair the ischemic insult of the
stroke
brain.
Results
: Activated
FOXC1
regulated the proliferation of APSCs in a cell cycle-dependent manner, whereas
FOXC1
-mediated APSCs self-renewal was abolished in
FOXC1
knockout mice (
FOXC1
-/-
mice). Moreover, upregulation of STI-1 regulated by
FOXC1
enhanced cell survival and self-renewal of APSCs through autocrine signaling of cellular prion protein (PrP
C
). Mouse brain explants STI-1 rescues the cortical phenotype
in vitro
and induces neurogenesis in the
FOXC1
-/-
mouse brain. Furthermore, administration of APSCs in ischemic brain restored the neuroglial microenvironment and improved neurological dysfunction.
Conclusion
: We identified a novel role for
FOXC1
in the direct regulation of the STI-1-PrP
C
signaling pathway to promote cell proliferation and self-renewal of APSCs.
...
PMID:Role of FOXC1 in regulating APSCs self-renewal via STI-1/PrP
C
signaling. 3158 28
