Unraveling the biomolecular effects of Mongolian mind-body interactive psychotherapy on psoriasis: An exosome proteomic analysis
Psoriasis is a chronic inflammatory skin disease etiologically related to stress. Mongolian mind-body interactive psychotherapy (MMIP) is a group psychotherapy that integrates traditional Mongolian medicine theory with modern psychology. Exosomes are nanovesicles that carry biomolecules such as proteins, and the lipid bilayer protects cargo from degeneration. The present study was conducted to discern the effects of MMIP on psoriasis from a biomolecular perspective, particularly by performing an exosome proteomic analysis. Plasma exosomes were extracted from 15 samples, derived from psoriasis patients (n = 5, before and after MMIP) and healthy controls (HCs; n = 5). All patients had spent 60 days engaging with MMIP. Proteomic analysis was conducted using high-throughput mass spectrometry, and the differentially expressed proteins (DEPs) were analyzed. Further, validation test was done in serum samples of psoriasis (n = 56) and HC (n = 29). After the MMIP, the psoriasis area and severity index improved by 75%. Compared to HCs, psoriasis patients demonstrated alterations in 41 DEPs, with significant involvement of ribosome and apelin/APJ pathway. The recovery of psoriasis following the therapy was found to be associated with significant alterations in 16 DEPs, involving pathways of Fc gamma-mediated receptor phagocytosis, tight junction, and vascular smooth muscle contraction. Notably, one of the immunoglobulins that were reduced in psoriasis was significantly elevated after the MMIP. Validation results showed that the levels of serum elafin were higher in psoriasis than in HC but significantly decreased after MMIP. In conclusion, this study demonstrated that MMIP has a significant influence on the profiles of immunoglobulins and inflammatory molecules, as well as several pathways participating in the psoriasis recovery, providing insights into the pathophysiology of psoriasis and possible potential therapeutic targets of the disease.
- World Health Organization. Global Report on Psoriasis. Geneva: World Health Organization; 2016.
- Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J Med. 2009;361(5):496-509. doi: 10.1056/NEJMra0804595
- Hall JMF, Cruser D, Podawiltz A, Mummert DI, Jones H, Mummert ME. Psychological stress and the cutaneous immune response: Roles of the HPA axis and the sympathetic nervous system in atopic dermatitis and psoriasis. Dermatol Res Pract. 2012;2012:403908. doi: 10.1155/2012/403908
- Rousset L, Halioua B. Stress and psoriasis. Int J Dermatol. 2018;57(10):1165-1172. doi: 10.1111/ijd.14032
- Schon MP, Wilsmann-Theis D. Current developments and perspectives in psoriasis. J Dtsch Dermatol Ges. 2023;21(4):363-372. doi: 10.1111/ddg.15033
- Rendon A, Schakel K. Psoriasis pathogenesis and treatment. Int J Mol Sci. 2019;20(6):1475. doi: 10.3390/ijms20061475
- Orsmond A, Bereza-Malcolm L, Lynch T, March L, Xue M. Skin barrier dysregulation in psoriasis. Int J Mol Sci. 2021;22(19):10841. doi: 10.3390/ijms221910841
- Albanesi C, Madonna S, Gisondi P, Girolomoni G. The interplay between keratinocytes and immune cells in the pathogenesis of psoriasis. Front Immunol. 2018;9:1549. doi: 10.3389/fimmu.2018.01549
- Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020;367(6478):eaau6977. doi: 10.1126/science.aau6977
- Yu H, Feng H, Zeng H, et al. Exosomes: The emerging mechanisms and potential clinical applications in dermatology. Int J Biol Sci. 2024;20(5):1778-1795. doi: 10.7150/ijbs.92897
- Xiong M, Zhang Q, Hu W, et al. Exosomes from adipose-derived stem cells: The emerging roles and applications in tissue regeneration of plastic and cosmetic surgery. Front Cell Dev Biol. 2020;8:574223. doi: 10.3389/fcell.2020.574223
- Kandimalla R, Aqil F, Tyagi N, Gupta R. Milk exosomes: A biogenic nanocarrier for small molecules and macromolecules to combat cancer. Am J Reprod Immunol. 2021;85(2):e13349. doi: 10.1111/aji.13349
- Gurung S, Perocheau D, Touramanidou L, Baruteau J. The exosome journey: From biogenesis to uptake and intracellular signalling. Cell Commun Signal. 2021;19(1):47. doi: 10.1186/s12964-021-00730-1
- Wei H, Chen Q, Lin L, et al. Regulation of exosome production and cargo sorting. Int J Biol Sci. 2021;17(1):163-177. doi: 10.7150/ijbs.53671
- Xiong M, Zhang Q, Hu W, et al. The novel mechanisms and applications of exosomes in dermatology and cutaneous medical aesthetics. Pharmacol Res. 2021;166:105490. doi: 10.1016/j.phrs.2021.105490
- McBride JD, Rodriguez-Menocal L, Badiavas EV. Extracellular vesicles as biomarkers and therapeutics in dermatology: A focus on exosomes. J Invest Dermatol. 2017;137(8):1622-1629. doi: 10.1016/j.jid.2017.04.021
- Jiang M, Fang H, Shao S, et al. Keratinocyte exosomes activate neutrophils and enhance skin inflammation in psoriasis. FASEB J. 2019;33(12):13241-13253. doi: 10.1096/fj.201900642R
- Bai G, Matsuba T, Niki T, Hattori T. Stimulation of THP-1 macrophages with LPS increased the production of osteopontin-encapsulating exosome. Int J Mol Sci. 2020;21(22):8490. doi: 10.3390/ijms21228490
- Chularojanamontri L, Charoenpipatsin N, Silpa-Archa N, Wongpraparut C, Thongboonkerd V. Proteomics in psoriasis. Int J Mol Sci. 2019;20(5):1141. doi: 10.3390/ijms20051141
- Reindl J, Pesek J, Krüger T, et al. Proteomic biomarkers for psoriasis and psoriasis arthritis. J Proteomics. 2016;140:55-61. doi: 10.1016/j.jprot.2016.03.040
- Xu M, Deng J, Xu K, et al. In-depth serum proteomics reveals biomarkers of psoriasis severity and response to traditional Chinese medicine. Theranostics. 2019;9(9):2475-2488. doi: 10.7150/thno.31144
- Chagan-Yasutan H, Arlud S, Zhang L, Hattori T, Heriyed B, He N. Mongolian Mind-Body Interactive Psychotherapy enhances the quality of life of patients with esophageal cancer: A pilot study. Complement Ther Clin Pract. 2020;38:101082. doi: 10.1016/j.ctcp.2019.101082
- He N, He, A. Mongolian Mind-Body interactive Psychotherapy. Hubei: Wuhan Hubei Science & Technology Press; 2015. (In Chinese)
- He N, Lan W, Jiang A, et al. New method for insomnia mongolian mind-body interactive psychotherapy in the assessment of chronic insomnia: A retrospective study. Adv Ther. 2018;35(7):993-1000. doi: 10.1007/s12325-018-0726-9
- He N. Phased achievement of mongolian mind-body interactive psychotherapy in treatment of psoriasis patients. J Med Pharm Chin Minorities. 2016;7. (In Chinese).
- Abrouk M, Nakamura M, Zhu TH, Farahnik B, Koo J, Bhutani T. The impact of PASI 75 and PASI 90 on quality of life in moderate to severe psoriasis patients. J Dermatolog Treat. 2017;28(6):488-491. doi: 10.1080/09546634.2016.1278198
- Gisondi P, Geat D, Bellinato F, et al. Psychological stress and salivary cortisol levels in patients with plaque psoriasis. J Pers Med. 2021;11(11):1069. doi: 10.3390/jpm11111069
- Snaith RP, Zigmond AS. HADS: Hospital Anxiety and Depression Scale. Windsor, UK: NFER Nelson; 1994.
- Ma J, Liu M, Wang Y, et al. Quantitative proteomics analysis of young and elderly skin with DIA mass spectrometry reveals new skin aging-related proteins. Aging (Albany NY). 2020;12(13):13529-13554. doi: 10.18632/aging.103461
- Gao F, Jiao F, Xia C, et al. A novel strategy for facile serum exosome isolation based on specific interactions between phospholipid bilayers and TiO2. Chem Sci. 2019;10(6):1579-1588.
- Cox J, Mann M. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat Biotechnol. 2008;26(12):1367-1372. doi: 10.1038/nbt.1511
- He M, Chen X, Luo M, et al. Suppressor of cytokine signaling 1 inhibits the maturation of dendritic cells involving the nuclear factor kappa B signaling pathway in the glioma microenvironment. Clin Exp Immunol. 2020;202(1):47-59. doi: 10.1111/cei.13476
- Chagan-Yasutan H, Ndhlovu LC, Lacuesta TL, et al. Galectin-9 plasma levels reflect adverse hematological and immunological features in acute dengue virus infection. J Clin Virol. 2013;58(4):635-640. doi: 10.1016/j.jcv.2013.10.022
- Chagan-Yasutan H, Ndhlovu LC, Lacuesta TL, et al. The elevation of plasma galectin-9 levels in patients with psoriasis and its associations with inflammatory and immune checkpoint molecules in skin tissues. Hum Immunol. 2024;85(1):110741. doi: 10.1016/j.humimm.2023.110741
- Pang B, Zhu Z, Xiao C, et al. Keratin 17 Is Required for lipid metabolism in keratinocytes and benefits epidermal permeability barrier homeostasis. Front Cell Dev Biol. 2021;9:779257. doi: 10.3389/fcell.2021.779257
- Rietscher K, Wolf A, Hause G, et al. Growth retardation, loss of desmosomal adhesion, and impaired tight junction function identify a unique role of plakophilin 1 in vivo. J Invest Dermatol. 2016;136(7):1471-1478. doi: 10.1016/j.jid.2016.03.021
- Standker L, Schrader M, Kanse SM, Jürgens M, Forssmann WG, Preissner KT. Isolation and characterization of the circulating form of human endostatin. FEBS Lett. 1997;420(2-3):129-133. doi: 10.1016/s0014-5793(97)01503-2
- Kakurina GV, Kolegova ES, Kondakova IV. Adenylyl cyclase-associated protein 1: Structure, regulation, and participation in cellular processes. Biochemistry (Mosc). 2018;83(1):45-53. doi: 10.1134/S0006297918010066
- Buommino E, De Filippis A, Gaudiello F, et al. Modification of osteopontin and MMP-9 levels in patients with psoriasis on anti-TNF-alpha therapy. Arch Dermatol Res. 2012;304(6):481-485. doi: 10.1007/s00403-012-1251-3
- Vianello E, Kalousová M, Dozio E, Tacchini L, Zima T, Romanelli MMC. Osteopontin: The molecular bridge between fat and cardiac-renal disorders. Int J Mol Sci. 2020;21(15):5568. doi: 10.3390/ijms21155568
- Plavina T, Hincapie M, Wakshull E, Subramanyam M, Hancock WS. Increased plasma concentrations of cytoskeletal and Ca2+-binding proteins and their peptides in psoriasis patients. Clin Chem. 2008;54(11):1805-1814. doi: 10.1373/clinchem.2008.103770
- Teixeira GG, Mari NL, de Paula JCC, et al. Cell adhesion molecules, plasminogen activator inhibitor type 1, and metabolic syndrome in patients with psoriasis. Clin Exp Med. 2020;20(1):39-48. doi: 10.1007/s10238-019-00595-2
- Nikolova B, Kostadinova A, Dimitrov B, et al. Fluorescent imaging for assessment of the effect of combined application of electroporation and rifampicin on HaCaT cells as a new therapeutic approach for psoriasis. Sensors (Basel). 2013;13(3):3625-3634. doi: 10.3390/s130303625
- Moll I, Kurzen H, Langbein L, Franke WW. The distribution of the desmosomal protein, plakophilin 1, in human skin and skin tumors. J Invest Dermatol. 1997;108(2):139-146. doi: 10.1111/1523-1747.ep12332388
- Claesson R, Kanasi E, Johansson A, Kalfas S. A new cleavage site for elastase within the complement component 3. APMIS. 2010;118(10):765-768. doi: 10.1111/j.1600-0463.2010.02655.x
- Holmannova D, Borsky P, Borska L, et al. Metabolic syndrome, clusterin and elafin in patients with psoriasis vulgaris. Int J Mol Sci. 2020;21(16):5617. doi: 10.3390/ijms21165617
- Szel E, Bozó R, Hunyadi-Gulyás É, et al. Comprehensive proteomic analysis reveals intermediate stage of non-lesional psoriatic skin and points out the importance of proteins outside this trend. Sci Rep. 2019;9(1):11382. doi: 10.1038/s41598-019-47774-5
- Rieg S, Garbe C, Sauer B, Kalbacher H, Schittek B. Dermcidin is constitutively produced by eccrine sweat glands and is not induced in epidermal cells under inflammatory skin conditions. Br J Dermatol. 2004;151(3):534-539. doi: 10.1111/j.1365-2133.2004.06081.x
- Bamburg JR. Proteins of the ADF/cofilin family: Essential regulators of actin dynamics. Annu Rev Cell Dev Biol. 1999;15:185-230. doi: 10.1146/annurev.cellbio.15.1.185
- Benz PM, Blume C, Seifert S, et al. Differential VASP phosphorylation controls remodeling of the actin cytoskeleton. J Cell Sci. 2009;122(Pt 21):3954-3965. doi: 10.1242/jcs.044537
- Vorselen D, Barger SR, Wang Y, et al. Phagocytic “teeth” and myosin-II “jaw” power target constriction during phagocytosis. Elife. 2021;10:e68627. doi: 10.7554/eLife.68627
- Jin ZL, Jo YJ, Namgoong S, Kim NH. CAP1-mediated actin cycling via ADF/cofilin proteins is essential for asymmetric division in mouse oocytes. J Cell Sci. 2018;131(23):jcs222356. doi: 10.1242/jcs.222356
- Herlin T, Borregaard N, Kragballe K. On the mechanism of enhanced monocyte and neutrophil cytotoxicity in severe psoriasis. J Invest Dermatol. 1982;79(2):104-108. doi: 10.1111/1523-1747.ep12500035
- Bernier GM. Adult hypogammaglobulinemia. Analysis of 100 cases. Am J Med. 1964;36:618-623. doi: 10.1016/0002-9343(64)90108-1
- Almutairi A, Amin MM, Rashwan MAM, et al. Digenic inheritance of IL-36RA and SEC61A1 mutations underlies generalized pustular psoriasis with hypogammaglobulinemia. Clin Immunol. 2022;235:108930. doi: 10.1016/j.clim.2022.108930
- Wu MN, Qin K, Iroegbu CD, et al. Genetic analysis of potential biomarkers and therapeutic targets in ferroptosis from psoriasis. Front Immunol. 2022;13:1104462. doi: 10.1111/jcmm.17239
- Shahine A, Van Rhijn I, Cheng TY, et al. A molecular basis of human T cell receptor autoreactivity toward self-phospholipids. Sci Immunol. 2017;2(16):eaao1384. doi: 10.1126/sciimmunol.aao1384
- Schalkwijk J, Chang A, Janssen P, De Jongh GJ, Mier PD. Skin-derived antileucoproteases (SKALPs): Characterization of two new elastase inhibitors from psoriatic epidermis. Br J Dermatol. 1990;122(5):631-641. doi: 10.1111/j.1365-2133.1990.tb07285.x
- Wiedow O, Schröder JM, Gregory H, Young JA, Christophers E. Elafin: An elastase-specific inhibitor of human skin. Purification, characterization, and complete amino acid sequence. J Biol Chem. 1990;265(25):14791-14795.
- Tanaka N, Fujioka A, Tajima S, Ishibashi A, Hirose S. Elafin is induced in epidermis in skin disorders with dermal neutrophilic infiltration: Interleukin-1 beta and tumour necrosis factor-alpha stimulate its secretion in vitro. Br J Dermatol. 2000;143(4):728-732. doi: 10.1046/j.1365-2133.2000.03766.x
- Alkemade HA, de Jongh GJ, Arnold WP, van de Kerkhof PC, Schalkwijk J. Levels of skin-derived antileukoproteinase (SKALP)/elafin in serum correlate with disease activity during treatment of severe psoriasis with cyclosporin A. J Invest Dermatol. 1995;104(2):189-193. doi: 10.1111/1523-1747.ep12612749
- Al’Abadie MS, Kent GG, Gawkrodger DJ. The relationship between stress and the onset and exacerbation of psoriasis and other skin conditions. Br J Dermatol. 1994;130(2):199-203. doi: 10.1111/j.1365-2133.1994.tb02900.x
- Neerackal RJ, Abdul Latheef EN, Sukumarakurup S, Jafferany M. Relaxation therapy in the management of psoriasis. Dermatol Ther. 2020;33(6):e14030. doi: 10.1111/dth.14030