Reducing‐Autophagy Derived Mitochondrial Dysfunction during Resveratrol Promotes Fibroblast‐Like Synovial Cell Apoptosis

Abstract

In rheumatoid arthritis patients, the fibroblast-like synovial cells (FLS) growth is not controlled normally, but is similar to the tumor cells proliferation in histology. Our previous studies have shown that resveratrol inhibits the proliferation of FLS and promotes FLS apoptosis. However, the molecular mechanisms involved in resveratrol-induced FLS apoptosis have not been determined yet. Here, we showed that the FLS cell viability (following pretreatment with 5 µM H O for 24 hr) exhibited better proliferation performance than at other concentrations via the CCK-8 assay. The cell apoptotic rate increased with the increasing concentration of resveratrol (0, 40, 80, 160, 320 μM), as detected by TdT-mediated dUTP nick-end labeling (TUNEL) staining and western blotting. Furthermore, the expression level of autophagy-related proteins (LC3A/B, ATG-5) decreased with the increased concentration of resveratrol, as determined by immunofluorescence and western blot analysis. We also showed that resveratrol induced FLS mitochondrial morphology change. Moreover, mitochondrial function detection showed that the mitochondrial membrane potential was lost with the increased concentration of resveratrol as examined by the JC-1 assay. The production of ATP in cells was positively and negatively correlated with the resveratrol concentration. Simultaneously, the intracellular calcium release and calcium influx decreased gradually with the increase in resveratrol concentration. Therefore, we proposed that resveratrol can reduce the level of autophagy in FLS. The decrease in the autophagy level can lead to the accumulation of reactive oxygen species, which may result in mitochondrial dysfunction and promotion of FLS apoptosis. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc.

Apoptosis Induction of Fibroblast-Like Synoviocytes Is an Important Molecular-Mechanism for Herbal Medicine along with its Active Components in Treating Rheumatoid Arthritis

“…Later, in 2018, it was also reported that Huangqichongteng Drink (HQCD) can induce the synovial cells in G0/G1 stage of cell growth, promoting apoptosis in RA-FLS [141]. Besides, it is also found resveratrol (9) (40-320 µM) down-regulated the autophagy related proteins (LC3A/B and ATG-5) in H 2 O 2 induced FLS cells, and increase the ROS production and Ca 2+ release, resulting in apoptosis of FLS [142]. Besides, it is reported that Wogonin (42), total glucosides of paeonia (TGP), Cinnamic aldehyde (CINA, 43), and Paclitaxel (44) also have pro-apoptosis effects on the RA-FLS [143][144][145][146].…”

Rapamycin‐Induced Autophagy Promotes the Chondrogenic Differentiation of Synovium‐Derived Mesenchymal Stem Cells in the Temporomandibular Joint in Response to IL‐1β

“…However, the role of autophagy in chondrogenesis is seldom reported in the literature. Moreover, decreased autophagy results in the accumulation of reactive oxygen species, which leads to mitochondrial dysfunction and promotes the apoptosis of synovial cells [ 4 ]. In contrast, the decreased levels of autophagy have been observed in the synovium of adjuvant arthritis rats, leading to the excessive proliferation of synovial cells [ 5 ].…”

“…At the same time, autophagy plays a regulatory role in stem cell proliferation and multidirectional differentiation. Studies have focused on the effects of autophagy with respect to chronic inflammation of the synovium[ 4 , 5 ]. However, whether autophagy plays a role in the chondrogenesis of SMSCs under inflammatory conditions has not yet been investigated.…”

Transcriptome Analysis of Juvenile Tilapia (Oreochromis niloticus) Blood, Fed With Different Concentrations of Resveratrol

“…It can regulate mitochondrial redox status, which in some cases prevents or delays disease progression ( Teixeira et al, 2019 ). RES can reduce the level of autophagy in the apoptosis (apoptosis pathway changed in the streptococcosis affected tilapia, Zhu et al, 2017 ) process by preventing the accumulation of reactive oxygen species in fibroblast-like synovial cells, which might result in mitochondrial dysfunction ( Cao et al, 2018 ). It has the potential to be used as an immunopotentiator in fish cultivation to determine the relationship between mitochondrial dysfunction and pathogenic prevention.…”