EXPERIMENTAL RESEARCH
The role of the STING inflammatory pathway in hepatic damage in psoriasis with type 2 diabetes mellitus
More details
Hide details
1
900th Hospital of Joint Logistic Support Force, Fuzong Clinical Medical College
These authors had equal contribution to this work
Submission date: 2023-12-15
Final revision date: 2024-01-21
Acceptance date: 2024-02-05
Online publication date: 2024-10-30
Corresponding author
Pin Chen
900TH Hospital of Joint Logistic Support Force, China
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Studies have suggested a potential association between patients who have both psoriasis and diabetes and liver damage. However, the exact nature of this link has not yet been fully established. The objective of the current study was to examine the potential exacerbation of liver damage due to the coexistence of psoriasis and type 2 diabetes mellitus (T2DM) and to explore the impact of interferon gene stimulating factor (STING) on related damage.
Material and methods:
Four patient groups were recruited: normal individuals, individuals with diabetes, those with psoriasis, and those with both diabetes and psoriasis. Relevant indicators were collected to facilitate the investigation. Furthermore, a mouse model of psoriasis combined with T2DM was established. The expression levels of STING and inflammatory factors downstream of the pathway were detected in both the skin and liver tissues of the model mice.
Results:
Based on our findings, patients with both psoriasis and T2DM exhibit abnormal liver function and increased STING expression in the skin (p < 0.05). In the in vivo experiments, liver tissues from model mice exhibited significantly elevated expression of STING and its downstream inflammatory factors, including NF-κB p65, interferon-β, interleukin (IL)-17A, and IL-23 (p < 0.05). The STING inhibitor-treated group displayed reduced skin damage and improved liver histopathology (p < 0.05).
Conclusions:
The findings of the current study indicate that the STING inflammatory pathway is upregulated in the liver tissues of individuals with psoriasis and T2DM.
REFERENCES (35)
1.
Perera GK, Di Meglio P, Nestle FO. Psoriasis. Annu Rev Pathol 2012; 7: 385-422.
2.
Korman NJ. Management of psoriasis as a systemic disease: what is the evidence? Br J Dermatol 2020; 182: 840-8.
3.
Lowes MA, Bowcock AM, Krueger JG. Pathogenesis and therapy of psoriasis. Nature 2007; 445: 866-73.
4.
Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med 2010; 49: 1603-16.
5.
Cariou B, Byrne CD, Loomba R, Sanyal AJ. Nonalcoholic fatty liver disease as a metabolic disease in humans: a literature review. Diabetes Obes Metab 2021; 23: 1069-83.
6.
Takezaki D, Morizane S, Ikeda K, et al. Co-occurrence of non-alcoholic steatohepatitis exacerbates psoriasis associated with decreased adiponectin expression in a murine model. Front Immunol 2023; 14: 1214623.
7.
Rachfal AW, Grant SFA, Schwartz SS. The diabetes syndrome – a collection of conditions with common, interrelated pathophysiologic mechanisms. Int J Gen Med 2021; 14: 923-36.
8.
D’Adamio S, Silvaggio D, Lombardo P, et al. The safety of anti-interleukins monoclonal antibodies for the treatment of psoriasis. Expert Opin Drug Saf 2019; 18: 1031-41.
9.
onne R, Saroul-Ainama M, Cordier P, et al. Replication stress triggered by nucleotide pool imbalance drives DNA damage and cGAS-STING pathway activation in NAFLD. Dev Cell 2022; 57: 1728-41.
10.
Wang X, Rao H, Zhao J, et al. STING expression in monocyte-derived macrophages is associated with the progression of liver inflammation and fibrosis in patients with nonalcoholic fatty liver disease. Lab Invest 2020; 100: 542-52.
11.
Xiaohong L, Zhenting Z, Yunjie Y, et al. Activation of the STING-IRF3 pathway involved in psoriasis with diabetes mellitus. J Cell Mol Med 2022; 26: 2139-51.
12.
Lin L, Xu X, Yu Y, et al. Glucagon-like peptide-1 receptor agonist liraglutide therapy for psoriasis patients with type 2 diabetes: a randomized-controlled trial. J Dermatolog Treat 2022; 33: 1428-34.
13.
Griffiths CEM, Armstrong AW, Gudjonsson JE, Barker J. Psoriasis. Lancet 2021; 397: 1301-15.
14.
Dattilo G, Borgia F, Guarneri C, et al. Cardiovascular risk in psoriasis: current state of the art. Curr Vasc Pharmacol 2018; 17: 85-91.
15.
Teklu M, Zhou W, Kapoor P, et al. Metabolic syndrome and its factors are associated with noncalcified coronary burden in psoriasis: an observational cohort study. J Am Acad Dermatol 2021; 84: 1329-38.
16.
Gau SY, Huang KH, Lee CH, et al. Bidirectional association between psoriasis and nonalcoholic fatty liver disease: real-world evidence from two longitudinal cohort studies. Front Immunol 2022; 13: 840106.
17.
Carrascosa JM, Vilarrasa E, Belinchón I, et al. Abordaje común del paciente con psoriasis y riesgo de esteatosis hepática metabólica: recomendaciones de un grupo de expertos multidisciplinar. Actas Dermosifiliogr 2023; 114: 392-401.
18.
Evans EA, Sayers SR, Kodji X, et al. Psoriatic skin inflammation induces a pre-diabetic phenotype via the endocrine actions of skin secretome. Mol Metab 2020; 41: 101047.
19.
Sivasami P, Elkins C, Diaz-Saldana PP, et al. Obesity-induced dysregulation of skin-resident PPARgamma(+) Treg cells promotes IL-17A-mediated psoriatic inflammation. Immunity 2023; 56: 1844-61.
20.
West AP, Khoury-Hanold W, Staron M, et al. Mitochondrial DNA stress primes the antiviral innate immune response. Nature 2015; 520: 553-7.
21.
Wu L, Guo X, Wong SY, et al. Deficiency of beta-carotene oxygenase 2 induces mitochondrial fragmentation and activates the STING-IRF3 pathway in the mouse hypothalamus. J Nutr Biochem 2021; 88: 108542.
22.
Liu Y, Lu X, Qin N, et al. STING, a promising target for small molecular immune modulator: a review. Eur J Med Chem 2021; 211: 113113.
23.
Wu JJ, Zhao L, Hu HG, et al. Agonists and inhibitors of the STING pathway: potential agents for immunotherapy. Med Res Rev 2020; 40: 1117-41.
24.
Zhang S, Zheng R, Pan Y, Sun H. Potential therapeutic value of the STING inhibitors. Molecules 2023; 28: 3127.
25.
Lv J, Xing C, Chen Y, et al. The STING in non-alcoholic fatty liver diseases: potential therapeutic targets in inflammation-carcinogenesis pathway. Pharmaceuticals 2022; 15: 1241.
26.
Chuang KC, Chang CR, Chang SH, et al. Imiquimod-induced ROS production disrupts the balance of mitochondrial dynamics and increases mitophagy in skin cancer cells. J Dermatol Sci 2020; 98: 152-62.
27.
Zhong F, Liang S, Zhong Z. Emerging role of mitochondrial DNA as a major driver of inflammation and disease progression. Trends Immunol 2019; 40: 1120-33.
28.
Rizwan H, Pal S, Sabnam S, Pal A. High glucose augments ROS generation regulates mitochondrial dysfunction and apoptosis via stress signalling cascades in keratinocytes. Life Sci 2020; 241: 117148.
29.
Petrasek J, Iracheta-Vellve A, Csak T, et al. STING-IRF3 pathway links endoplasmic reticulum stress with hepatocyte apoptosis in early alcoholic liver disease. Proc Natl Acad Sci USA 2013; 110: 16544-9.
30.
Luo X, Li H, Ma L, et al. Expression of STING is increased in liver tissues from patients with NAFLD and promotes macrophage-mediated hepatic inflammation and fibrosis in mice. Gastroenterology 2018; 155: 1971-84.
31.
Ellulu MS, Patimah I, Khaza’ai H, et al. Obesity and inflammation: the linking mechanism and the complications. Arch Med Sci 2017; 13: 851-63.
32.
Murdaca G, Colombo BM, Puppo F. The role of Th17 lymphocytes in the autoimmune and chronic inflammatory diseases. Intern Emerg Med 2011; 6: 487-95.
33.
Li YN, Su Y. Remdesivir attenuates high fat diet (HFD)-induced NAFLD by regulating hepatocyte dyslipidemia and inflammation via the suppression of STING. Biochem Biophys Res Commun 2020; 526: 381-8.
34.
Iracheta-Vellve A, Petrasek J, Gyongyosi B, et al. Endoplasmic reticulum stress-induced hepatocellular death pathways mediate liver injury and fibrosis via stimulator of interferon genes. J Biol Chem 2016; 291: 26794-805.
35.
Thomsen MK, Nandakumar R, Stadler D, et al. Lack of immunological DNA sensing in hepatocytes facilitates hepatitis B virus infection. Hepatology 2016; 64: 746-59.