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: UNIPROT:P01034 (
cystatin C
)
3,397
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Cystatin C, a well-established biomarker of renal function, has been associated with a protective effect against stroke. However, the potential neuroprotective mechanism of
cystatin C
in ischemic brain injury remains unclear. Our study hypothesized that
cystatin C
can ameliorate blood-brain barrier (BBB) disruption by up-regulating caveolin-1 expression, thereby improving neurological outcomes in cerebral ischemic injury. Western blotting, immunohistochemistry, immunofluorescence staining, and immunoprecipitation were performed to investigate target proteins.
Evans Blue
and gelatin zymography were used to examine the effect of
cystatin C
on BBB disruption. Plasmid and small interfering RNA transfection was used to observe alterations in caveolin-1 and occludin expression induced by changes in
cystatin C
expression. Intriguingly, our study showed that the expression of both
cystatin C
and caveolin-1 was increased in middle cerebral artery occlusion-injured mice, and pretreatment with exogenous
cystatin C
significantly increased caveolin-1 expression, reduced
Evans Blue
leakage in the injured brain region, and decreased the enzymatic activity of matrix metallopeptidase-9. Meanwhile, our study also showed that the over-expression of
cystatin C
greatly enhanced caveolin-1 expression, which later increased occludin expression in oxygen-glucose deprivation-exposed brain microvascular endothelial cells. The knockdown of
cystatin C
induced the opposite outcomes. These experimental results indicate a positive role for
cystatin C
in the regulation of caveolin-1 and occludin expression in cerebral ischemic injury. Taken together, these data unveil a new mechanism of the regulation of caveolin-1 expression by
cystatin C
in the maintenance of BBB integrity after ischemic brain injury and provide new clues for the identification of potential therapeutic strategies for stroke.
...
PMID:Cystatin C improves blood-brain barrier integrity after ischemic brain injury in mice. 3160 90
