Anesthesiology Department, Cangzhou Central Hospital, Cangzhou, Hebei Province, P.R. China.
Ophthalmology Department, Cangzhou Central Hospital, Cangzhou, Hebei Province, P.R. China.
Arch Physiol Biochem. 2024 Oct;130(5):529-536. doi: 10.1080/13813455.2023.2190054. Epub 2023 Apr 19.
:The aim of our study was to determine the molecular mechanism of BMP4 (bone morphogenetic protein 4) in DR (diabetic retinopathy).: Human retinal endothelial cell (HRECs) induced by high glucose to simulate one of the pathogenesis in the diabetic retinopathy (DR) model. RT-qPCR and western blot were used to detect the mRNA and protein levels of BMP4 in the STZ/HG group. Flow cytometry and TUNEL staining were performed to detect the apoptosis. Angiogenesis was evaluated by tube formation assay. Transwell assay and wound healing assay were used to detect cell migration ability. H&E staining was used to evaluate the pathological changes.: BMP4 was significantly upregulated in the STZ/HG group. Sh-BMP4 significantly inhibited the migration and angiogenesis of RVECs induced by HG. In addition, both in vivo and in vitro experiments confirmed that sh-BMP4 could significantly promote RVECs apoptosis in the HG/STZ group. Western blot results showed that sh-BMP4 could down-regulate the expressions of p-smad1, p-smad5 and VEGF.: Inhibition of BMP4 could alleviate the damage of diabetic retinopathy by regulating the p-smad1/5/VEGF signaling axis, inhibiting angiogenesis and promoting apoptosis.
:本研究旨在探讨 BMP4(骨形态发生蛋白 4)在 DR(糖尿病性视网膜病变)中的分子机制。:高糖诱导人视网膜内皮细胞(HRECs)模拟糖尿病性视网膜病变(DR)模型的一种发病机制。采用 RT-qPCR 和 Western blot 检测 STZ/HG 组中 BMP4 的 mRNA 和蛋白水平。流式细胞术和 TUNEL 染色检测细胞凋亡。通过管形成试验评估血管生成。Transwell 试验和划痕愈合试验用于检测细胞迁移能力。H&E 染色用于评估病理变化。:STZ/HG 组中 BMP4 明显上调。Sh-BMP4 显著抑制 HG 诱导的 RVECs 的迁移和血管生成。此外,体内和体外实验均证实,sh-BMP4 可显著促进 HG/STZ 组中 RVECs 的凋亡。Western blot 结果表明,sh-BMP4 可下调 p-smad1、p-smad5 和 VEGF 的表达。:抑制 BMP4 可通过调节 p-smad1/5/VEGF 信号通路,抑制血管生成和促进细胞凋亡,从而减轻糖尿病性视网膜病变的损伤。