Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin 300384, China.
Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin 300384, China.
Exp Biol Med (Maywood). 2020 Jun;245(11):956-963. doi: 10.1177/1535370220919056. Epub 2020 May 3.
The detailed molecular mechanism of orbital venous malformation (OVM) is still not clear. Using whole exome sequencing, 4 types of melanocortin 4 receptor (MC4R) mutation were detected in 7 of 27 patients with OVM, and all types of MC4R mutations resulted in the upregulation of MC4R expression. study indicated that MC4R has impacts on the proliferation, cell cycle, migration, and tube formation of the endothelial cells. Moreover, MC4R mutations altered the downstream signaling, including cAMP concentration and the expression levels of several PI3K/AKT/mTOR downstream genes, including p21, cyclin B1, ITGA10, and ITGA11. MC4R mutations may lead to the pathogenesis of OVM through modulating the downstream signaling to alter the angiogenic activity of endothelial cells.
眼眶静脉畸形（OVM）的详细分子机制尚不清楚。通过全外显子组测序，在 27 例 OVM 患者中检测到 4 种黑素皮质素 4 受体（MC4R）突变，所有类型的 MC4R 突变均导致 MC4R 表达上调。研究表明，MC4R 对内皮细胞的增殖、细胞周期、迁移和管形成有影响。此外，MC4R 突变改变了下游信号，包括 cAMP 浓度和几个 PI3K/AKT/mTOR 下游基因的表达水平，包括 p21、周期蛋白 B1、ITGA10 和 ITGA11。MC4R 突变可能通过调节下游信号改变内皮细胞的血管生成活性，从而导致 OVM 的发病机制。
