Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Mol Biol Rep. 2022 May;49(5):3721-3728. doi: 10.1007/s11033-022-07212-8. Epub 2022 Feb 3.
Asthma, an inflammatory illness of the lungs, remains the most common long-term disease amongst children. This study tried to elaborate the status of apoptosis in asthmatic pulmonary niche after the application of rat mesenchymal stem cells (MSC-CM)-derived secretome.
Here, we randomly allocated male Wistar rats into three groups (n = 8); Control animals were intratracheally given 50 μl vehicle. In control-matched sensitized rats, 50 μl normal saline was used. In the last group, 50 μl MSC-CM was applied. Two-week post-administration, transcription of T-bet, GATA-3, Bax, Bcl-2 and Caspase-3 was measured by gene expression analysis. Pathological injuries were monitored using H&E staining. The BALF level of TNF-α was measured using ELISA assay. In asthmatic rats received MSC-CM, the expression of T-bet was increased while the level of GATA-3 decreased compared to the S group (p < 0.05). Levels of BALF TNF-α were suppressed in asthmatic niche after MSC-CM administration (p < 0.05). Compared to the asthmatic group, MSC-CM had potential to alter the expression of apoptosis-related genes in which the expression of Bax and Caspase 3 was decreased and the expression of pro-survival factor, Bcl-2 increased (p < 0.05).
Our data notified the potency of direct administration of MSC-CM in the alleviation of airway inflammation, presumably by down regulating apoptotic death in pulmonary niche.
哮喘是一种肺部炎症性疾病,仍是儿童中最常见的慢性疾病。本研究试图阐述大鼠间充质干细胞(MSC-CM)衍生的分泌组应用后哮喘肺龛中的细胞凋亡状态。
我们将雄性 Wistar 大鼠随机分为三组(n=8);对照组气管内给予 50μl 载体。在对照匹配的致敏大鼠中,使用 50μl 生理盐水。在最后一组中,应用 50μl MSC-CM。给药后 2 周,通过基因表达分析测量 T-bet、GATA-3、Bax、Bcl-2 和 Caspase-3 的转录。通过 H&E 染色监测病理损伤。使用 ELISA 测定 BALF 中 TNF-α 的水平。在接受 MSC-CM 的哮喘大鼠中,与 S 组相比,T-bet 的表达增加,而 GATA-3 的水平降低(p<0.05)。在 MSC-CM 给药后,哮喘龛中的 BALF TNF-α 水平受到抑制(p<0.05)。与哮喘组相比,MSC-CM 有可能改变与细胞凋亡相关的基因表达,其中 Bax 和 Caspase 3 的表达降低,而生存因子 Bcl-2 的表达增加(p<0.05)。
我们的数据通知了直接给予 MSC-CM 缓解气道炎症的潜力,可能通过下调肺龛中的细胞凋亡死亡。