Department of Occupational and Environmental Health Science, College of Public Health, Zhengzhou University, Zhengzhou, Henan province, 450001, China.
Mol Biol Rep. 2023 Sep;50(9):7215-7224. doi: 10.1007/s11033-023-08590-3. Epub 2023 Jul 7.
Fibrosis is a response to ongoing cellular injury, disruption, and tissue remodeling, the pathogenesis of which is unknown, and is characterized by extracellular matrix deposition. The antifibrotic effect of Geranylgeranylacetone (GGA), as an inducer of Heat shock protein 70 (HSP70), in liver, kidney and pulmonary fibrosis has been supported by multiple preclinical evidence. However, despite advances in our understanding, the precise roles of HSP70 in fibrosis require further investigation. The purpose of this study was to investigate whether GGA could participate in the progression of pulmonary fibrosis in mice through apoptosis, oxidative stress and inflammation.
B-cell lymphoma-2(Bcl-2) and Bcl2-Associated X (Bax) are two proteins related to apoptosis. Anti-apoptotic factor Bcl-2 and pro-apoptotic factor Bax are often involved in the apoptotic process in the form of dimer. Immunofluorescence and Western blot results showed that bleomycin (BLM) and transforming growth factor-β (TGF-β) inhibited Bcl-2 expression and promoted Bax expression in vitro and in vivo, respectively. In contrast, GGA treatment reverses this change. Reactive oxygen species (ROS), Malondialdehyde (MDA) and superoxide dismutase (SOD) are markers of oxidative stress, which often reflect oxidative injury of cells. The detection of ROS, MDA and SOD expression showed that TGF-β and BLM treatment could significantly promote oxidative stress, while GGA treatment could alleviate oxidative stress damage. In addition, BLM significantly elevated Tumor necrosis factor-α(TNF-α), Interleukin1β (IL-1β) and Interleukin 6 (IL-6), while scutellarin reversed the above alterations except for that of GGA.
Taken together, GGA suppressed apoptotic, oxidative stress and inflammation in BLM-induced pulmonary fibrosis.
纤维化是对持续的细胞损伤、破坏和组织重塑的反应，其发病机制尚不清楚，其特征是细胞外基质沉积。先前的临床前证据表明，香叶基丙酮（GGA）作为热休克蛋白 70（HSP70）的诱导剂，具有抗纤维化作用，可用于治疗肝、肾和肺纤维化。然而，尽管我们对纤维化的认识有所提高，但 HSP70 在纤维化中的确切作用仍需要进一步研究。本研究旨在探讨 GGA 是否通过细胞凋亡、氧化应激和炎症参与小鼠肺纤维化的进展。
B 细胞淋巴瘤-2（Bcl-2）和 Bcl2 相关 X（Bax）是两种与细胞凋亡相关的蛋白。抗凋亡因子 Bcl-2 和促凋亡因子 Bax 通常以二聚体的形式参与凋亡过程。免疫荧光和 Western blot 结果表明，博来霉素（BLM）和转化生长因子-β（TGF-β）分别在体外和体内抑制 Bcl-2 的表达并促进 Bax 的表达。相比之下，GGA 处理可逆转这种变化。活性氧（ROS）、丙二醛（MDA）和超氧化物歧化酶（SOD）是氧化应激的标志物，它们通常反映细胞的氧化损伤。ROS、MDA 和 SOD 表达的检测表明，TGF-β和 BLM 处理可显著促进氧化应激，而 GGA 处理可减轻氧化应激损伤。此外，BLM 可显著升高肿瘤坏死因子-α（TNF-α）、白细胞介素 1β（IL-1β）和白细胞介素 6（IL-6），而黄芩素可逆转上述改变，除了 GGA 以外。
综上所述，GGA 抑制 BLM 诱导的肺纤维化中的细胞凋亡、氧化应激和炎症。
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