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Global Translational Medicine Resveratrol’s EC barrier protection is dependent on KLF2

higher rate of EBD incorporation into the tissue, suggesting within the endothelium. These complexes are categorized
an overall increase in barrier dysfunction with resveratrol’s as either tight junctions, which seal the endothelium and
protective effect being completely abolished (Figure 4). limit paracellular diffusion, or adherens junctions, which
These findings clearly identify KLF2 as a necessary regulate EC cell-cell contacts, cytoskeletal association, and
downstream mediator of resveratrol and an important intracellular signaling . To maintain cerebral homeostasis
[13]
regulator of its vasculoprotective effects. and prevent blood-borne molecules from entering
the brain, it is essential to maintain a strict separation
4. Discussion between the blood and extravascular compartments .
[14]
The blood–brain barrier (BBB) is a critical structural Proteins that contribute to the endothelial barrier function
and biochemical barrier composed of the endothelium (i.e., claudins, occludin, and JAMs) are critical in the
and the surrounding extracellular matrix. The properties maintenance of BBB integrity. Hence, the disruption of
of the BBB are primarily due to junctional complexes these proteins contributes to a broad spectrum of disease

A B

Figure 3. Resveratrol has endothelial barrier protective effects, with this barrier protective function being Krϋppel-like factor 2 dependent. (A) In vitro
permeability analysis quantifying passage of fluorescein isothiocyanate (FITC)-dextran across primary human brain microvascular ECs pre-treated with
resveratrol (100 μM for 16 h) or vehicle at baseline (Control) and after 30 min oxygen-glucose deprivation, followed by 2 h of normal media (n = 3/group).
(B) Permeability assessment as in (A) using cells transfected with small interfering ribonucleic acid (siRNA, si-NS or siKLF2) (n = 4 per group). NS: Non-
specific siRNA. *P < 0.05; ***P < 0.001; ****P < 0.0001.

A

B

Figure 4. Blood–brain barrier (BBB) protection effect of resveratrol is Krϋppel-like factor 2 (KLF2) dependent. (A) Schematic diagram for in vivo BBB
studies. (B) Quantification of Evans blue dye permeability of brains harvested from control and KLF2 knockout mice after pretreatment with vehicle or
resveratrol (75 mg/kg) through gastric gavage for 10 days (n = 6/group). Control: CAG-CreERT , KLF2-/-: postnatal KLF2 knockout, Res: Resveratrol.
2
**P < 0.005; ***P < 0.001.

Volume 2 Issue 1 (2023) 5 https://doi.org/10.36922/gtm.v2i1.218