Mechanisms of catalpol regulation of RASF against RA via MAPK/GBP5 signaling pathway

Volume 7, Issue 2, April 2022     |     PP. 56-65      |     PDF (477 K)    |     Pub. Date: May 14, 2022
DOI: 10.54647/biology18219    69 Downloads     5808 Views  

Author(s)

Mei Jie, Shandong Police General Hospital, China
He Qiang, Nanjing Hospital of Traditional Chinese Medicine, affiliated with Nanjing University of Traditional Chinese Medicine, China
Zhang Dapeng, Nanjing Hospital of Traditional Chinese Medicine, affiliated with Nanjing University of Traditional Chinese Medicine, China
Sun Xin, Nanjing Hospital of Traditional Chinese Medicine, affiliated with Nanjing University of Traditional Chinese Medicine, China

Abstract
Objective: Synovial fibroblasts (RASF) in rheumatoid arthritis are important mediators of synovial inflammation and joint destruction. This study provides valuable suggestions for the prevention and treatment of RA by observing catalase intervention in RASF and exploring its possible mechanisms.
Methods: An in vitro model of interleukin (IL)-1β-induced inflammatory synovial fibroblasts was established, and cells were intervened with different concentrations of catalpol (0, 20, 40, 60, 80, 100, 120, 140 μmol/L) for 6 h. Cell activity was measured by the CCK8 method; cells were divided into a blank group, a model group, a low dose of catalpol (20 μmol/L) group, a high dose of catalpol (100 μmol/L) group, and a high dose of catalpol (100 μmol/L) group. （The cells were divided into blank group, model group, catalpol low dose group (20 μmol/L), catalpol high dose group (100 μmol/L) and positive control group (methotrexate 100 nmol/L), and treated with different concentrations of catalpol (0 μmol/L, 20 μmol/L, 100 μmol/L) and methotrexate (100 nmol/L) for 2 h. The cells were then stimulated with IL-1β (20 ng) for 6 h. The cell supernatants were assayed by enzyme-linked immunosorbent assay (ELISA). The cell supernatant TNF-α, IL-6 and IL-17 contents were measured by ELISA kit; the protein expression levels of p-p38/p38, p-ERK/ERK, p-JNK/JNK and GBP5 in the cells were detected by protein immunoblotting (Western blotting).
Result: Compared with the blank group, the levels of TNF-α, IL-6, IL-17 and the protein expression of p-p38/p38, p-ERK/ERK, p-JNK/JNK, GBP5 were increased in the model group cells (P < 0.05); compared with the model group, the catalase low and high groups (concentrations of 20 μmol/L and 100 μmol/L, respectively) and the positive control Cells (methotrexate 100 nmol/L) showed decreased TNF-α, IL-6, IL-17 content and protein expression of p-p38/p38, p-ERK/ERK, p-JNK/JNK, GBP5 (P < 0.05). Compared with the blank group, the cell activities of the model group, catalpol low dose group (10 μmol/L) and positive control group were decreased, while the catalpol high dose group (100 μmol/L) had increased cell activities.
Conclusion: The results of in vitro cellular assays suggest that catalpol can inhibit inflammatory RASF and may be related to the inhibition of MAPK/GBP5 signaling-mediated pro-inflammatory cytokine release, and that catalpol has potential therapeutic value in RA.

Keywords
Catalponol; rheumatoid arthritis; synovial fibroblasts

Cite this paper
Mei Jie, He Qiang, Zhang Dapeng, Sun Xin, Mechanisms of catalpol regulation of RASF against RA via MAPK/GBP5 signaling pathway , SCIREA Journal of Biology. Volume 7, Issue 2, April 2022 | PP. 56-65. 10.54647/biology18219

References

[ 1 ] Wang Meiling, Zhang Leiming, Hao Yanfei, et al. Protective effect of gentian bitter glycosides on rheumatoid arthritis and its mechanism[J]. Chinese Journal of Pharmacology and Toxicology, 2019, 33(9):1.
[ 2 ] Tsai CY, Hsieh SC, Liu CW, et al. The Expression of Non-Coding RNAs and Their Target Molecules in Rheumatoid Arthritis: A Molecular Basis for Rheumatoid Pathogenesis and Its Potential Clinical Applications[J]. Int J Mol Sci. 2021;22(11):5689.
[ 3 ] CHEN Wenjia, LI Taixian, WANG Xiaoyue, et al. Meta-analysis of the clinical efficacy of methotrexate alone or in combination with Leigongjiang polysaccharide tablets in the treatment of rheumatoid arthritis[J]. Chinese Journal of Traditional Chinese Medicine, 2020(4):791-797.
[ 4 ] Zhang Yifeng, Ye Xiuling, Duan Meng, et al. Comparison of clinical characteristics of rheumatoid arthritis in the elderly and young adults[J]. Chinese Journal of Medicine, 2020, 100(47):3788-3792.
[ 5 ] He Q, Mei J, Qian WQ, et al. Systematic evaluation of the effectiveness of herbal medicines to tonify the kidney and invigorate blood in treating osteoarthritis of the knee with liver and kidney deficiency [J]. Clinical Research in Chinese Medicine, 2020, 12(27):44-49.
[ 6 ] He Qiang, Yin Hong, Dai Fenglei, et al. Effect of Dihuangzhiol on the expression of S100A12, IL-1β, and Galectin-3 levels in synovial tissues of a rat knee osteoarthritis model induced by papain [J]. Chinese Journal of Immunology, 2020, 34(21):2597-2602.
[ 7 ] Chinese Pharmacopoeia 2015 edition. Part I [S]. 2015.
[ 8 ] He Q, Qian WQ, Yao NW, et al. Protective effect of Dihuangziol on inflammatory osteoblasts in neonatal rats[J]. Chinese Tissue Engineering Research, 2020, 24(29):4626-4631.
[ 9 ] Jiang M. Chinese rheumatology [M]. Huaxia Publishing House, 2004.
[ 10 ] Kemble S, Croft AP. Critical Role of Synovial Tissue-Resident Macrophage and Fibroblast Subsets in the Persistence of Joint Inflammation[J]. Front Immunol. 2021;12:715894.
[ 11 ] SONG Xian-Bing, CHEN Xiao-Yu, HUANG Yan-Ping, et al. Apoptosis-inducing effects of resveratrol on fibroblast-like synovial cells in AA rats and possible mechanisms[J]. Chinese Journal of Pharmacology, 2020, 036(005):660-665.
[ 12 ] Liu Y, Wang YP, Liu M, et al. Isochlorogenic acid A inhibits TNF-α-induced proliferation and migration of MH7A human fibroblast-like synoviocytes and promotes their apoptosis[J]. Journal of Cellular and Molecular Immunology, 2020, v.36(08):25-30.
[ 13 ] Wang Y, Khan A, Antonopoulos A, et al. Loss of α2-6 sialylation promotes the transformation of synovial fibroblasts into a pro-inflammatory phenotype in arthritis[J]. Nat Commun. 2021;12(1):2343.
[ 14 ] Malaquias A C , Jorge A . Activation of the MAPK pathway (RASopathies) and partial growth hormone insensitivity[J]. Molecular and Cellular Endocrinology, 2021, 519:111040.
[ 15 ] Wu XY, Zhang GR. Study on the inflammation of human synovial cells and its therapeutic effects on rheumatoid arthritis through NF-κB and MAPK signaling pathways[J]. Journal of Guangxi Medical University. 2020;37(9):1636-1641.
[ 16 ] Grześk G, Nowaczyk A. Current Modulation of Guanylate Cyclase Pathway Activity-Mechanism and Clinical Implications[J]. Molecules. 2021;26(11):3418.
[ 17 ] Zhang R, Li Z, Tang YD, et al. When human guanylate-binding proteins meet viral infections[J]. J Biomed Sci. 2021;28(1):17.
[ 18 ] Place DE, Malireddi RKS, Kim J, et al. Osteoclast fusion and bone loss are restricted by interferon inducible guanylate binding proteins[J]. Nat Commun. 2021;12(1):496.
[ 19 ] Feng, X. Mechanism of influenza A virus-induced guanylate-binding protein 5 (GBP5) regulation of viral replication[D]. Wuhan University, 2017.
[ 20 ] Haque M , Singh A K , Ouseph M M , et al. Guanylate Binding Protein 5 (GBP5) regulates synovial fibroblast mediated inflammation and tissue destruction in rheumatoid arthritis[J]. Arthritis & Rheumatology, 2020.
[ 21 ] Cheng SW, Chen PC, Ger TR, et al. GBP5 Serves as a Potential Marker to Predict a Favorable Response in Triple-Negative Breast Cancer Patients Receiving a Taxane-Based Chemotherapy. J Pers Med[J]. 2021;11(3):197.
[ 22 ] Cheng SW, Chen PC, Lin MH, et al. GBP5 Repression Suppresses the Metastatic Potential and PD-L1 Expression in Triple-Negative Breast Cancer[J]. Biomedicines. 2021;9(4):371.