Microcirculation (New York, N.Y. : 1994) · 2026
IL-17 Promotes the Phenotypic Transformation of Vascular Smooth Muscle Cells Through PI3K/AKT Signaling Pathway.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Yao Song, Fu Tianfu, Tu Qingxian, Zhang Jie, Jiang Qianfeng, Xu Min, Wang Zhenglong, Jiao Yang, Tian Haixia
Аннотация
BACKGROUND: Salt-sensitive hypertension (SSH) is associated with phenotypic changes in vascular smooth muscle cells (VSMCs). This study aimed to investigate the role of interleukin-17 (IL-17) in SSH and its impact on VSMC phenotype, focusing on the PI3K/AKT signaling pathway.
METHODS: In vivo, an SSH rat model was established. Systolic blood pressure (SBP) was monitored, and mesenteric artery tissues were collected for ex vivo histological and immunohistochemical analysis. In vitro, VSMCs were isolated from the arteries. Lentiviral vectors were used to knock down or overexpress IL-17 in these cells. Cell viability, migration, and invasion were assessed using CCK-8, scratch, and Transwell assays, respectively. Phosphorylation status was analyzed using a RayBiotech antibody array. Protein expression and phosphorylation levels were analyzed by Western blotting.
RESULTS: In vivo, SSH model rats developed hypertension and exhibited VSMC phenotypic transformation in mesenteric arteries. In vitro, VSMCs from SSH model rats showed elevated IL-17 expression. Knockdown of IL-17 in these cells suppressed their hyper-proliferative, migratory, and invasive phenotype and reversed the expression changes of contractile (α-actin and calponin) and synthetic (osteopontin) markers. This was associated with inhibition of PI3K/AKT phosphorylation. Conversely, IL-17 overexpression in control VSMCs recapitulated the pathological phenotype, which was blocked by the PI3K/AKT inhibitor Wortmannin (WM).
CONCLUSION: IL-17 promotes the phenotypic transformation of VSMCs in SSH through the PI3K/AKT signaling pathway. Inhibition of IL-17 or the PI3K/AKT pathway may represent a therapeutic strategy for SSH.
METHODS: In vivo, an SSH rat model was established. Systolic blood pressure (SBP) was monitored, and mesenteric artery tissues were collected for ex vivo histological and immunohistochemical analysis. In vitro, VSMCs were isolated from the arteries. Lentiviral vectors were used to knock down or overexpress IL-17 in these cells. Cell viability, migration, and invasion were assessed using CCK-8, scratch, and Transwell assays, respectively. Phosphorylation status was analyzed using a RayBiotech antibody array. Protein expression and phosphorylation levels were analyzed by Western blotting.
RESULTS: In vivo, SSH model rats developed hypertension and exhibited VSMC phenotypic transformation in mesenteric arteries. In vitro, VSMCs from SSH model rats showed elevated IL-17 expression. Knockdown of IL-17 in these cells suppressed their hyper-proliferative, migratory, and invasive phenotype and reversed the expression changes of contractile (α-actin and calponin) and synthetic (osteopontin) markers. This was associated with inhibition of PI3K/AKT phosphorylation. Conversely, IL-17 overexpression in control VSMCs recapitulated the pathological phenotype, which was blocked by the PI3K/AKT inhibitor Wortmannin (WM).
CONCLUSION: IL-17 promotes the phenotypic transformation of VSMCs in SSH through the PI3K/AKT signaling pathway. Inhibition of IL-17 or the PI3K/AKT pathway may represent a therapeutic strategy for SSH.