Exosomal miR‐3131 derived from endothelial cells with KRAS mutation promotes EndMT by targeting PICK1 in brain arteriovenous malformations

He, Qiheng; Huo, Ran; Wang, Jie; Xu, Hongyuan; Zhao, Shufang; Zhang, Junze; Sun, Yingfan; Jiao, Yuming; Weng, Jian-Cong; Zhao, Jizong; Cao, Yong

doi:10.1111/cns.14103

Cited by 6 publications

(2 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…24 During the EndMT, certain endothelial markers may be lost or retained in parallel to the acquisition of mesenchymal markers and morphology. [25][26][27][28] Li et al [29][30][31][32] recently reported that KRAS mutations regulate the EndMT in cerebral arteriovenous malformations, and KLF4 was described as a key determinant of the EndMT in cerebral cavernous malformations. Although the EndMT contributes to a variety of cerebrovascular disorders, its role in MMD remains unclear.…”

Section: Introductionmentioning

confidence: 99%

“…The endothelial‐to‐mesenchymal transition (EndMT) is a process through which endothelial cells acquire mesenchymal phenotypes, while losing their endothelial characteristics 24 . During the EndMT, certain endothelial markers may be lost or retained in parallel to the acquisition of mesenchymal markers and morphology 25–28 . Li et al 29–32 …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

High glutamine increases stroke risk by inducing the endothelial‐to‐mesenchymal transition in moyamoya disease

He,

Li,

Tao

et al. 2024

MedComm

Self Cite

View full text Add to dashboard Cite

At present, there is limited research on the mechanisms underlying moyamoya disease (MMD). Herein, we aimed to determine the role of glutamine in MMD pathogenesis, and 360 adult patients were prospectively enrolled. Human brain microvascular endothelial cells (HBMECs) were subjected to Integrin Subunit Beta 4 (ITGB4) overexpression or knockdown and atorvastatin. We assessed factors associated with various signaling pathways in the context of the endothelial‐to‐mesenchymal transition (EndMT), and the expression level of related proteins was validated in the superficial temporal arteries of patients. We found glutamine levels were positively associated with a greater risk of stroke (OR = 1.599, p = 0.022). After treatment with glutamine, HBMECs exhibited enhanced proliferation, migration, and EndMT, all reversed by ITGB4 knockdown. In ITGB4‐transfected HBMECs, the MAPK–ERK–TGF–β/BMP pathway was activated, with Smad4 knockdown reversing the EndMT. Furthermore, atorvastatin suppressed the EndMT by inhibiting Smad1/5 phosphorylation and promoting Smad4 ubiquitination in ITGB4‐transfected HBMECs. We also found the protein level of ITGB4 was upregulated in the superficial temporal arteries of patients with MMD. In conclusion, our study suggests that glutamine may be an independent risk factor for hemorrhage or infarction in patients with MMD and targeting ITGB4 could potentially be therapeutic approaches for MMD.

show abstract