Department of Medical Physiology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Department of Medical Biochemistry, Faculty of Medicine, Alexandria University, Alexandria, Egypt; Molecular Biology and Nanomedicine Labs, Centre of Excellence for Regenerative Medicine Research & Applications, University of Alexandria, Alexandria, Egypt.
Life Sci. 2022 Nov 15;309:120988. doi: 10.1016/j.lfs.2022.120988. Epub 2022 Sep 22.
Pulmonary fibrosis (PF) is considered as an end stage for many lung diseases. Mesenchymal stem cells (MSC) as regenerative therapy have become a remarkably valuable therapeutic strategy in different diseases. Hydrogen sulfide has been recently introduced into the medical field for its antifibrotic properties in addition to enhancement of MSC stemness and function. The aim of the present study was to investigate the ability of BM-MSC in combination with NaHS to attenuate Bleomycin induced pulmonary fibrosis was studied in rats. A special emphasis was given to miR-21 and GAS5 as important players in the development of PF.
PF was induced in 32 Wistar male rats by single endotracheal injection of bleomycin, those were randomly divided into four groups (8 rats each): (untreated PF group) - (PF + MSC) treated group- (PF + NaHS treated group) - PF + combined (NAHS + MSC) treated group.
Induction of PF was associated with increased miR-21 and decreased lncRNA-GAS5 expression. Treatment with either NaHS or BM-MSC leads to an inhibitory effect on pulmonary fibrosis as evidenced by improvement of histopathological studies, pulmonary function tests, reduction of inflammatory and fibrotic markers like Hydroxyproline, TNF α, TGF-β and caspase -3 together with downregulation miR-21 and increase lncRNA-GAS5 expression.
The current work revealed the inhibitory effect of combined NaHS and BM-MSC on pulmonary fibrosis with concomitant modulation of miR-21 and lncRNA-GAS5 expression.
肺纤维化（PF）被认为是许多肺部疾病的终末期。间充质干细胞（MSC）作为再生疗法，在多种疾病中已成为一种极具价值的治疗策略。硫化氢因其抗纤维化特性以及增强 MSC 干性和功能，最近被引入医学领域。本研究旨在研究骨髓间充质干细胞（BM-MSC）与 NaHS 联合应用对博莱霉素诱导的大鼠肺纤维化的抑制作用。特别强调了 miR-21 和 GAS5 在 PF 发展中的重要作用。
通过单次气管内注射博莱霉素诱导 32 只 Wistar 雄性大鼠 PF，将其随机分为四组（每组 8 只）：（未治疗 PF 组）-（PF+MSC 治疗组）-（PF+NaHS 治疗组）-PF+联合（NaHS+MSC）治疗组。
PF 的诱导与 miR-21 的增加和 lncRNA-GAS5 表达的减少有关。无论是 NaHS 还是 BM-MSC 治疗都可通过改善组织病理学研究、肺功能测试、降低羟脯氨酸、TNFα、TGF-β 和半胱天冬酶-3 等炎症和纤维化标志物，以及下调 miR-21 和增加 lncRNA-GAS5 表达，对肺纤维化产生抑制作用。
本研究揭示了联合应用 NaHS 和 BM-MSC 对肺纤维化的抑制作用，并同时调节 miR-21 和 lncRNA-GAS5 的表达。
