11β-HSD1 REGULATES GLUT1 EXPRESSION IN HUMAN BRAIN MICROVASCULAR ENDOTHELIAL CELLS

Öz

11β‑Hydroxysteroid dehydrogenase type 1 (11β‑HSD1) locally regenerates active glucocorticoids and has been linked to metabolic dysfunction and neurodegeneration. In this study, we aimed to investigate whether 11β-HSD1, an enzyme known to modulate glucocorticoid activity and metabolic homeostasis, plays a regulatory role in the expression of glucose transporter-1 (GLUT1) in human brain microvascular endothelial cells (HBEC5-i), which are critical for maintaining blood–brain barrier integrity and cerebral energy balance. HBEC5‑i were transduced with a GFP‑tagged pLKO.1 lentiviral vector (MOI 10) encoding an shRNA against 11β‑HSD1 or with a non‑targeting control. Transduction efficiency was confirmed by GFP fluorescence and knockdown was validated by immunoblotting. Protein abundance of GLUT1, CPT1A, PFKFB3 and GSK3α/β was quantified by western blotting. 11β‑HSD1 knockdown reduced GLUT1 and GSK3α/β while CPT1A and PFKFB3 remained unchanged. While the association between 11β-HSD1 and energy metabolism is well-documented, the precise molecular mechanisms governing this relationship remain incompletely understood. Our study is the first to explore this interaction specifically in HBEC5‑i, providing foundational insights that not only elucidate the metabolic roles of 11β-HSD1 in this unique cellular context but also pave the way for future research aimed at uncovering the downstream signaling pathways and therapeutic potential of targeting 11β-HSD1 in cerebrovascular disorders.

Anahtar Kelimeler

• 11β‑HSD1
• GLUT1
• Brain microvascular endothelial cells
• Energy metabolism
• Blood–brain barrier

Kaynakça

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