Li Kang, Shen Chongyang, Wen Nianchi, Han Yicen, Guo Lu
Department of Gastroenterology, People's Hospital of Tibet Autonomous Region, Lhasa, Tibet 850000, China.
School of basic medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 230041, Sichuan, China.
Heliyon. 2024 Feb 7;10(4):e25234. doi: 10.1016/j.heliyon.2024.e25234. eCollection 2024 Feb 29.
To investigate whether erythropoietin (EPO) can treat pulmonary arterial hypertension (PAH) in rats by regulating the differentiation and homing of bone marrow mesenchymal stem cells (BMSCs) through Notch1/Jagged signaling pathway.
MATERIALS & METHODS: BMSCs were isolated from the bone marrow of 6-week-old male SD rats by whole bone marrow method and identified. BMSCs were treated with 500 IU/mL EPO, and the proliferation, migration, invasion and differentiation ability, and the expression of MMP-2 and MMP-9 protein of BMSCs were detected . After the establishment of the pulmonary hypertension model in rats, BMSCs were intervened with different concentrations of EPO and injected into the rats through intravenous injection. The levels of TNF-α, IL-1β and IL-6 in lung tissue, the expression of SRY CXCR4, CCR2, Notch1 and Jagged protein in lung tissue, and the levels of TGF-α, vascular endothelial factor (VEGF), IGF-1 and HGF in serum were detected. Immunofluorescence (IF) staining was used to detect the co-localization of CD34.
EPO promoted the proliferation, migration, and invasion of BMSCs by inhibiting Notch1/Jagged pathway , and induced BMSCs to differentiate into vascular smooth muscle cells and vascular endothelial cells. EPO inhibited Notch1/Jagged pathway in PAH rats, induced BMSCs homing and differentiation, increased the levels of TGF-α, VEGF, IGF-1 and HGF, and decreased the levels of TNF-α, IL-1β and IL-6.
DISCUSSION & CONCLUSION: EPO can inhibit the Notch1/Jagged pathway and promote the proliferation, migration, invasion, homing and differentiation of BMSCs to treat pulmonary hypertension in rats and .
探讨促红细胞生成素（EPO）是否可通过Notch1/锯齿蛋白信号通路调节骨髓间充质干细胞（BMSCs）的分化与归巢，从而治疗大鼠肺动脉高压（PAH）。
采用全骨髓法从6周龄雄性SD大鼠骨髓中分离并鉴定BMSCs。用500 IU/mL EPO处理BMSCs，检测BMSCs的增殖、迁移、侵袭和分化能力以及MMP-2和MMP-9蛋白的表达。建立大鼠肺动脉高压模型后，用不同浓度的EPO干预BMSCs并经静脉注射入大鼠体内。检测肺组织中TNF-α、IL-1β和IL-6的水平、肺组织中SRY、CXCR4、CCR2、Notch1和锯齿蛋白的表达以及血清中TGF-α、血管内皮生长因子（VEGF）、胰岛素样生长因子-1（IGF-1）和肝细胞生长因子（HGF）的水平。采用免疫荧光（IF）染色检测CD34的共定位。
EPO通过抑制Notch1/锯齿蛋白信号通路促进BMSCs的增殖、迁移和侵袭，并诱导BMSCs分化为血管平滑肌细胞和血管内皮细胞。EPO抑制PAH大鼠的Notch1/锯齿蛋白信号通路，诱导BMSCs归巢和分化，提高TGF-α、VEGF、IGF-1和HGF水平，降低TNF-α、IL-1β和IL-6水平。
EPO可抑制Notch1/锯齿蛋白信号通路，促进BMSCs的增殖、迁移、侵袭、归巢和分化，从而治疗大鼠肺动脉高压。
