STK39 is associated with endothelial dysfunction and inflammatory activation under hypoxic conditions in moyamoya disease.
6 affiliations
- 1Jiujiang City Key Laboratory of Cell Therapy, The First Hospital of Jiujiang City, Jiujiang, China.
- 2Department of Neurosurgery, The First Hospital of Jiujiang City, Jiujiang, China.
- 3Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
- 4China National Clinical Research Center for Neurological Diseases, Beijing, China.
- 5Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
- 6Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, United States.
Abstract
Moyamoya disease (MMD) is a cerebrovascular disease whose mechanism relatively unknown and can cause vascular occlusion and hyperplasia. This study aimed to explore molecular heterogeneity associated with the expression of acetylation-related genes in MMD and to identify candidate genes potentially involved in vascular endothelial dysfunction. Public MMD transcriptomic datasets were analyzed using a predefined acetylation-regulatory gene set to identify expression clusters and prioritize cluster-associated candidate genes. Functional enrichment, immune-infiltration, and predicted miRNA-mRNA network analyses were performed to characterize candidate-associated molecular features. Serum STK39 and MTMR12 concentrations were assessed by ELISA in a preliminary study of three patients with MMD and three healthy controls. STK39 was further investigated in human brain microvascular endothelial cells (HBMECs) using siRNA-mediated knockdown under normoxic and hypoxic conditions, with Trichostatin A (TSA) treatment included as an exploratory pharmacological intervention. Consensus clustering was used to classify MMD into two subtypes, and five key subtype-related genes were identified: STK39, NEO1, PKNOX1, GOLT1B, and MTMR12. In the validation cohort, serum STK39 and MTMR12 levels were significantly decreased in patients with MMD. In vitro, STK39 knockdown promoted HBMEC migration, inhibited proliferation, and increased the expression of HIF-1α, p-STAT3, cleaved Caspase-3, IL-6, CCL2, and VCAM-1 under hypoxic conditions, whereas TSA treatment partially reversed these changes. Acetylation-related genes are closely associated with the molecular heterogeneity of MMD. Among them, STK39 appears to participate in hypoxia-related endothelial dysfunction and inflammatory activation. These findings provide new insight into the role of acetylation-related pathways in MMD pathogenesis and suggest potential targets for future mechanistic studies.
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BibTeX
@article{liang2026stk39,
title = {{STK39 is associated with endothelial dysfunction and inflammatory activation under hypoxic conditions in moyamoya disease.}},
author = {Rui Liang and Zhenyu Zhou and Yaoren Chang and Xun Ye and Youjia Tang and Shihao He and Yuanli Zhao},
journal = {Frontiers in human neuroscience},
year = {2026},
month = oct,
doi = {10.3389/fnhum.2026.1854099},
url = {https://europepmc.org/article/MED/42953106},
note = {CC BY},
}
RIS
TY - JOUR
TI - STK39 is associated with endothelial dysfunction and inflammatory activation under hypoxic conditions in moyamoya disease.
AU - Rui Liang
AU - Zhenyu Zhou
AU - Yaoren Chang
AU - Xun Ye
AU - Youjia Tang
AU - Shihao He
AU - Yuanli Zhao
PY - 2026
DA - 2026/10/14
JO - Frontiers in human neuroscience
DO - 10.3389/fnhum.2026.1854099
UR - https://europepmc.org/article/MED/42953106
AB - Moyamoya disease (MMD) is a cerebrovascular disease whose mechanism relatively unknown and can cause vascular occlusion and hyperplasia. This study aimed to explore molecular heterogeneity associated with the expression of acetylation-related genes in MMD and to identify candidate genes potentially involved in vascular endothelial dysfunction. Public MMD transcriptomic datasets were analyzed using a predefined acetylation-regulatory gene set to identify expression clusters and prioritize cluster-associated candidate genes. Functional enrichment, immune-infiltration, and predicted miRNA-mRNA network analyses were performed to characterize candidate-associated molecular features. Serum STK39 and MTMR12 concentrations were assessed by ELISA in a preliminary study of three patients with MMD and three healthy controls. STK39 was further investigated in human brain microvascular endothelial cells (HBMECs) using siRNA-mediated knockdown under normoxic and hypoxic conditions, with Trichostatin A (TSA) treatment included as an exploratory pharmacological intervention. Consensus clustering was used to classify MMD into two subtypes, and five key subtype-related genes were identified: STK39, NEO1, PKNOX1, GOLT1B, and MTMR12. In the validation cohort, serum STK39 and MTMR12 levels were significantly decreased in patients with MMD. In vitro, STK39 knockdown promoted HBMEC migration, inhibited proliferation, and increased the expression of HIF-1α, p-STAT3, cleaved Caspase-3, IL-6, CCL2, and VCAM-1 under hypoxic conditions, whereas TSA treatment partially reversed these changes. Acetylation-related genes are closely associated with the molecular heterogeneity of MMD. Among them, STK39 appears to participate in hypoxia-related endothelial dysfunction and inflammatory activation. These findings provide new insight into the role of acetylation-related pathways in MMD pathogenesis and suggest potential targets for future mechanistic studies.
SN - 1662-5161
ER -