普萘洛尔通过阻断肥大细胞β-肾上腺素能受体抑制血管瘤内皮细胞的血管生成能力。
Propranolol inhibits the angiogenic capacity of hemangioma endothelia via blocking β-adrenoceptor in mast cell.
机构信息
Department of Dermatology, Children's Hospital of Fudan University &National Children Medical Center, Shanghai, China.
Department of Pediatric Institute, Children's Hospital of Fudan University &National Children Medical Center, Shanghai, China.
出版信息
Pediatr Res. 2022 Aug;92(2):424-429. doi: 10.1038/s41390-021-01683-4. Epub 2021 Oct 14.
BACKGROUND
Propranolol, a non-selective blocker of the β-adrenoceptor (AR), is a first-line treatment for infantile hemangioma (IH). Mast cells have been implicated in the pathophysiology of propranolol-treated hemangioma. However, the function of mast cells remains unclear.
METHODS
HMC-1s (Human mast cell line) having been treated with propranolol for 24 h were centrifuged, washed with PBS twice, and maintained in cell culture medium for another 24 h. The supernatants with propranolol which were named as propranolol-treated HMC-1s supernatants were obtained. The expression of cytokines and mediators was examined among HMC-1s dealt with propranolol. HemECs (hemangioma endothelial cells) were co-cultured with propranolol-treated HMC-1s supernatants, and their proliferation and apoptosis were investigated. The autophagic-related protein was examined in HemECs using immunoblot.
RESULTS
In propranolol-treated HMC-1s, the expressions of ADRB1 (β1-AR) and ADRB2 (β2-AR) were reduced by 70% and 60%, respectively, and that of cytokines and mediators were reduced. The proliferation was decreased, but apoptosis and autophagy were induced in HemECs treated with propranolol-treated HMC-1s supernatants. However, propranolol can work well in shRNA-ADRB1 or shRNA-ADRB2 transfected HMC-1s.
CONCLUSIONS
Propranolol inhibit the proliferation of HemECs and promote their apoptosis and autophagy through acting on both β1 and β2 adrenoceptor in mast cell.
IMPACT
Treated with propranolol, β1, and β2 adrenoceptor on human mast cell expression was reduced significantly. After hemangioma endothelial cell treated with the supernatants from propranolol-treated human mast cell, its proliferation was decreased, but apoptosis and autophagy were significantly induced. Propranolol can work well in shRNA-ADRB1 or shRNA-ADRB2 transfected HMC-1s. Mast cells may have a role in the action of propranolol in infantile hemangioma through both β1 and β2 adrenoceptors to inhibit the angiogenic capacity of hemangioma endothelial cells.
背景
普萘洛尔是一种非选择性β肾上腺素受体（AR）阻滞剂，是治疗婴儿血管瘤（IH）的一线药物。肥大细胞已被认为与普萘洛尔治疗的血管瘤的病理生理学有关。然而，肥大细胞的功能仍不清楚。
方法
用普萘洛尔处理 24 小时的 HMC-1s（人肥大细胞系）离心，用 PBS 洗涤两次，并用细胞培养液再维持 24 小时。获得含有普萘洛尔的上清液，命名为普萘洛尔处理的 HMC-1s 上清液。检测用普萘洛尔处理的 HMC-1s 中的细胞因子和介质的表达。将 HemECs（血管瘤内皮细胞）与普萘洛尔处理的 HMC-1s 上清液共培养，研究其增殖和凋亡情况。用免疫印迹法检测 HemECs 中的自噬相关蛋白。
结果
在普萘洛尔处理的 HMC-1s 中，ADRB1（β1-AR）和 ADRB2（β2-AR）的表达分别减少了 70%和 60%，细胞因子和介质的表达也减少了。HemECs 用普萘洛尔处理的 HMC-1s 上清液处理后，增殖减少，但凋亡和自噬增加。然而，在 shRNA-ADRB1 或 shRNA-ADRB2 转染的 HMC-1s 中，普萘洛尔仍能发挥良好的作用。
结论
普萘洛尔通过作用于肥大细胞上的β1 和β2 肾上腺素受体，抑制 HemECs 的增殖，促进其凋亡和自噬。
影响
用普萘洛尔处理后，人肥大细胞上的β1 和β2 肾上腺素受体表达显著降低。用普萘洛尔处理的人肥大细胞上清液处理 HemECs 后，其增殖减少，但凋亡和自噬明显增加。在 shRNA-ADRB1 或 shRNA-ADRB2 转染的 HMC-1s 中，普萘洛尔仍能发挥良好的作用。肥大细胞可能通过β1 和β2 肾上腺素受体在普萘洛尔治疗婴儿血管瘤中发挥作用，抑制血管瘤内皮细胞的血管生成能力。
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