PloS one · 2026
Long noncoding RNA Gpr137b-ps mediates 15-PGDH-induced angiogenesis in brain microvasculature following tMCAO in mice.
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Wang Di, Zhang Guojian, Gou Haiyan, Wang Yawei, Liang Wenye, Cao Yangyue, Jiao Yujuan
Аннотация
BACKGROUND: Angiogenesis is essential for recovery following ischemic stroke, as brain microvascular endothelial cells (BMVECs) drive vascular repair. 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is a major regulator of endothelial function in some vascular contexts, but it is unknown whether 15-PGDH plays a significant role in angiogenesis following stroke. Notably, based on preliminary bioinformatics prediction of their 3'UTR interaction, we hypothesize that Gpr137b-ps-a pseudogene-derived lncRNA originating from Gpr137b-forms a regulatory link with 15-PGDH to modulate this process (i.e., post-stroke angiogenesis) by regulating 15-PGDH expression, though its specific functional mechanism in this context remains largely unknown.
METHODS: To address this gap, we used mouse middle cerebral artery occlusion (MCAO) model in vivo and BMVEC oxygen-glucose deprivation/reoxygenation (OGD/R) model in vitro. We modulated 15-PGDH via siRNA and Gpr137b-ps via mimics, and assessed angiogenesis using migration, tube formation, and cell-cycle assays, with expression and localization of key molecules verified by standard molecular techniques.
RESULTS: Both MCAO and OGD/R successfully induced ischemia, with significant upregulation of 15-PGDH and Gpr137b-ps in ischemic tissues and BMVECs (P < 0.05). Despite this concurrent upregulation, 15-PGDH promoted angiogenesis (silencing reduced BMVEC proliferation, migration, and tube formation; P < 0.01), whereas Gpr137b-ps overexpression suppressed 15-PGDH protein levels and inhibited angiogenesis-effects that were rescued by re-expressing 15-PGDH.
CONCLUSION: Together, our findings identify Gpr137b-ps/15-PGDH as a key feedback regulatory axis: while both Gpr137b-ps and 15-PGDH are upregulated under ischemia, Gpr137b-ps (a negative regulator of angiogenesis) suppresses 15-PGDH (a pro-angiogenic factor) to repress excessive post-stroke angiogenesis via inhibiting BMVEC proliferation, migration, and cell-cycle progression. The data support an association and partial dependency between this axis and angiogenic processes, highlighting it as a potential therapeutic target (e.g., via inhibiting Gpr137b-ps) for vascular repair after ischemic stroke.
METHODS: To address this gap, we used mouse middle cerebral artery occlusion (MCAO) model in vivo and BMVEC oxygen-glucose deprivation/reoxygenation (OGD/R) model in vitro. We modulated 15-PGDH via siRNA and Gpr137b-ps via mimics, and assessed angiogenesis using migration, tube formation, and cell-cycle assays, with expression and localization of key molecules verified by standard molecular techniques.
RESULTS: Both MCAO and OGD/R successfully induced ischemia, with significant upregulation of 15-PGDH and Gpr137b-ps in ischemic tissues and BMVECs (P < 0.05). Despite this concurrent upregulation, 15-PGDH promoted angiogenesis (silencing reduced BMVEC proliferation, migration, and tube formation; P < 0.01), whereas Gpr137b-ps overexpression suppressed 15-PGDH protein levels and inhibited angiogenesis-effects that were rescued by re-expressing 15-PGDH.
CONCLUSION: Together, our findings identify Gpr137b-ps/15-PGDH as a key feedback regulatory axis: while both Gpr137b-ps and 15-PGDH are upregulated under ischemia, Gpr137b-ps (a negative regulator of angiogenesis) suppresses 15-PGDH (a pro-angiogenic factor) to repress excessive post-stroke angiogenesis via inhibiting BMVEC proliferation, migration, and cell-cycle progression. The data support an association and partial dependency between this axis and angiogenic processes, highlighting it as a potential therapeutic target (e.g., via inhibiting Gpr137b-ps) for vascular repair after ischemic stroke.