Abstract:Objective To explore the expression and clinical significance of phosphorylated protein kinase B (p-AKT), B-lymphoma-2 (Bcl-2) and matrix metalloproteinase-9 (MMP-9) in synovial tissues of patients with rheumatoid arthritis (RA). Methods Fifteen patients with RA who were hospitalized in orthopedics department of General Hospital of Eastern Theater Command from March 2013 to March 2022 were included in the RA group, while 10 patients with joint injuries who underwent knee surgeries during the same period were included in the control group. Synovial histopathological specimens and clinical data of RA patients were collected. Synovial tissue characteristics were assessed from a pathological perspective. Immunohistochemical staining was used to detect the expression of p-AKT, Bcl-2 and MMP-9 proteins in the synovial tissues of RA patients. Results There was no significant difference in age or gender between two groups (P>0.05). White blood cells (WBC), monocytes (MONO), neutrophils (NEUT), c-reactive protein (CPR), rheumatoid factors (RF) and anti-cyclic citrullinated peptide antibody (Anti-CCP) in RA group were significantly higher than those in the control group (P<0.05 or P<0.01). The Krenn’s pathological score of synovial tissues in the RA group was significantly higher than that in the control group (P<0.05 or P<0.01). Compared with the control group, the expressions of p-AKT, Bcl-2 and MMP-9 in the synovial tissue of the RA group were significantly higher than those of the control group (P<0.05 or P<0.01). The expression of p-AKT was positively correlated with ESR (r=0.680, P=0.005) and DAS28-3 (r=0.634, P=0.011). The expression of Bcl-2 was positively correlated with erythrocyte sedimentation rate (ESR) (r=0.640, P=0.010) and CRP (r=0.584, P=0.022). The expression of MMP-9 was positively correlated with ESR (r=0.809, P=0.000) and Disease Activity Score 28-3 (DAS28-3) (r=0.590, P=0.021). The expression of Bcl-2 and MMP-9 was positively correlated (r=0.630, P=0.012). Conclusions The expressions of p-AKT, Bcl-2 and MMP-9 increase in the synovial tissues of RA patients, which is positively correlated with indicators related with RA disease activity. The Overproliferation of synovium in RA patients may be related with the activation of AKT-related signaling pathways and the overexpression of apoptosis inhibitory protein Bcl-2.
Sparks J A. Rheumatoid arthritis [J]. Ann Intern Med, 2019, 170(1): ITC1-ITC16.
[2]
Masoumi M, Bashiri H, Khorramdelazad H, et al. Destructive roles of fibroblast-like synoviocytes in chronic inflammation and joint damage in rheumatoid arthritis [J]. Inflammation, 2021, 44(2): 466-479.
[3]
Sun K, Luo J, Guo J, et al. The PI3K/AKT/mTOR signaling pathway in osteoarthritis: a narrative review [J]. Osteoarthritis Cartilage, 2020, 28(4): 400-409.
[4]
Aihaiti Y, Tuerhong X, Zheng H, et al. Peroxiredoxin 4 regulates tumor-cell-like characteristics of fibroblast-like synoviocytes in rheumatoid arthritis through PI3k/Akt signaling pathway [J]. Clin Immunol, 2022,237:108964.
[5]
Hoxhaj G, Manning B D. The PI3K-AKT network at the interface of oncogenic signalling and cancer metabolism [J]. Nat Rev Cancer, 2020, 20(2): 74-88.
[6]
Kay J, Upchurch K S. ACR/EULAR 2010 rheumatoid arthritis classification criteria [J]. Rheumatology (Oxford), 2012, 51 (Suppl 6): vi5-9.
[7]
Balsa A, Carmona L, González-Alvaro I, et al. Value of disease activity score 28 (DAS28) and DAS28-3 compared to American college of rheumatology-defined remission in rheumatoid arthritis [J]. J Rheumatol, 2004, 31(1): 40-46.
[8]
Almutairi K, Nossent J, Preen D, et al. The global prevalence of rheumatoid arthritis: a meta-analysis based on a systematic review [J]. Rheumatol Int, 2021, 41(5): 863-877.
[9]
Weyand C M, Goronzy J J. The immunology of rheumatoid arthritis [J]. Nat Immunol, 2021, 22(1): 10-18.
[10]
Cush J J. Rheumatoid arthritis: early diagnosis and treatment [J]. Med Clin North Am, 2021, 105(2): 355-365.
[11]
Deane K D, Holers V M. Rheumatoid arthritis pathogenesis, prediction, and prevention: an emerging paradigm shift [J]. Arthritis Rheumatol, 2021, 73(2): 181-193.
[12]
Liu S, Ma H, Zhang H, et al. Recent advances on signaling pathways and their inhibitors in rheumatoid arthritis [J]. Clin Immunol, 2021, 230: 108793.
[13]
Ba X, Huang Y, Shen P, et al. WTD attenuating rheumatoid arthritis via suppressing angiogenesis and modulating the PI3K/AKT/mTOR/HIF-1α pathway [J]. Front Pharmacol, 2021, 12: 696802.
[14]
Cheng Q, Chen M, Liu M, et al. Semaphorin 5A suppresses ferroptosis through activation of PI3K-AKT-mTOR signaling in rheumatoid arthritis [J]. Cell Death Dis, 2022, 13(7): 608.
[15]
Zhang G, Liu H B, Zhou L, et al. CCL3 participates in the development of rheumatoid arthritis by activating AKT [J]. Eur Rev Med Pharmacol Sci, 2018, 22(20): 6625-6632.
[16]
Zhao J, Jiang P, Guo S, et al. Apoptosis, autophagy, NETosis, necroptosis, and pyroptosis mediated programmed cell death as targets for innovative therapy in rheumatoid arthritis [J]. Front Immunol, 2021, 12: 809806.
[17]
Alamgeer, Hasan U H, Uttra A M, et al. Phytochemicals targeting matrix metalloproteinases regulating tissue degradation in inflammation and rheumatoid arthritis[J]. Phytomedicine, 2020,66:153134.
[18]
Liang Z, Wang N, Shang L, et al. Evaluation of the immune feature of ACPA-negative rheumatoid arthritis and the clinical value of matrix metalloproteinase-3 [J]. Front Immunol, 2022, 13: 939265.
[19]
Grillet B, Yu K, Ugarte B E, et al. Proteoform analysis of matrix metalloproteinase-9/gelatinase B and discovery of its citrullination in rheumatoid arthritis synovial fluids [J]. Front Immunol, 2021, 12: 763832.
[20]
Radu A F, Bungau S G. Management of rheumatoid arthritis: an overview [J]. Cells, 2021, 10(11): 2857.