Fatty acid-binding protein 5 aggravates psoriasis and psoriasis-like disease through ferroptosis

Fatty acid-binding protein 5 aggravates psoriasis and psoriasis-like disease through ferroptosis

  • Skayem C, Taieb C, Halioua B, Baissac C, Saint AM. Epidemiology of Psoriasis: a worldwide global study. Acta Derm Venereol. 2025;105:2–4.

    Article 

    Google Scholar
     

  • Parisi R, Symmons DPM, Griffiths CEM, Ashcroft DM. Global epidemiology of psoriasis: a systematic review of incidence and prevalence. J Investig Dermatol. 2013;133:377–85.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Greb JE, Goldminz AM, Elder JT, Lebwohl MG, Gladman DD, Wu JJ, et al. Psoriasis. Nat Rev Dis Primers. 2016;2:1–17.

  • Fernández-AJM, Arbonés G, Buti-SM, Betriu BA, Sanmartin NV, Ortega BM, et al. Psoriasis, metabolic syndrome and cardiovascular risk factors. a population-based study. J Eur Acad Dermatol Venereol. 2019;33:128–35.

    Article 

    Google Scholar
     

  • Husni ME, Schwartzman S, Podobnik J, Garg A, Gottlieb AB. Correlation of high-density lipoprotein–associated paraoxonase 1 activity with systemic inflammation, disease activity, and cardiovascular risk factors in psoriatic disease. Arthritis Rheumatol. 2018;70:1240–50.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ryan C, Korman NJ, Gelfand JM, Lim HM, Elmets CA, Feldman SR, et al. Research gaps in psoriasis: opportunities for future studies. J Am Acad Dermatol. 2014;70:146–67.

    Article 
    PubMed 

    Google Scholar
     

  • Boehncke WH, Gladman DD, Chandran V. Cardiovascular comorbidities in psoriasis and psoriatic arthritis: pathogenesis, consequences for patient management, and future research agenda: a report from the GRAPPA 2009 annual meeting. J Rheumatol. 2011;38:567–71.

    Article 
    PubMed 

    Google Scholar
     

  • Conrad N, Verbeke G, Molenberghs G, Goetschalckx L, Callender T, Cambridge G, et al. Autoimmune diseases and cardiovascular risk: a population-based study on 19 autoimmune diseases and 12 cardiovascular diseases in 22 million individuals in the UK. Lancet. 2022;400:733–43.

    Article 
    PubMed 

    Google Scholar
     

  • Abuabara K, Azfar RS, Shin DB, Neimann AL, Troxel AB, Gelfand JM. Cause-specific mortality in patients with severe psoriasis: a population-based cohort study in the U.K. Br J Dermatol. 2010;163:586–592.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Menter A, Gottlieb A, Feldman SR, Van Voorhees AS, Leonardi CL, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol. 2008;58:826–50.

    Article 
    PubMed 

    Google Scholar
     

  • Meyer N, Paul C, Feneron D, Bardoulat I, Thiriet C, Camara C, et al. Psoriasis: an epidemiological evaluation of disease burden in 590 patients. J Eur Acad Dermatol Venereol. 2010;24:1075–82.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Rapp SR, Feldman SR, Exum ML, Fleischer AB, Reboussin DM. Psoriasis causes as much disability as other major medical diseases. J Am Acad Dermatol. 1999;41:401–7.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Snekvik I, Smith CH, Nilsen TIL, Langan SM, Modalsli EH, Romundstad PR, et al. Obesity, waist circumference, weight change, and risk of incident psoriasis: prospective data from the HUNT Study. J Investig Dermatol. 2017;137:2484–90.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Alotaibi HA. Effects of weight loss on psoriasis: a review of clinical trials. Cureus. 2018;10:5–11.


    Google Scholar
     

  • Naldi L, Conti A, Cazzaniga S, Patrizi A, Pazzaglia M, Lanzoni A, et al. Diet and physical exercise in psoriasis: a randomized controlled trial. Br J Dermatol. 2014;170:634–42.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Jensen P, Zachariae C, Christensen R, Geiker NR, Schaadt BK, Stender S, et al. Effect of weight loss on the severity of psoriasis: a randomized clinical study. JAMA Dermatol. 2013;149:795–801.

    Article 
    PubMed 

    Google Scholar
     

  • Kamiya K, Kishimoto M, Sugai J, Komine M, Ohtsuki M, Ohtsuki M. Risk factors for the development of psoriasis. Int J Mol Sci. 2019;20:1–14.

    Article 

    Google Scholar
     

  • Griffiths CEM, Armstrong AW, Gudjonsson JE, Barker JNWN. Psoriasis. Lancet. 2021;397:1301–15.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhou X, Chen Y, Cui L, Shi Y, Guo C. Advances in the pathogenesis of psoriasis: from keratinocyte perspective. Cell Death Dis. 2022;13:1–13.

  • Zhou Q, Mrowietz U, Rostami-Yazdi M. Oxidative stress in the pathogenesis of psoriasis. Free Radic Biol Med. 2009;47:891–905.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Jarocka-Karpowicz I, Biernacki M, Wroński A, Gęgotek A, Skrzydlewska E. Cannabidiol effects on phospholipid metabolism in keratinocytes from patients with psoriasis vulgaris. Biomolecules. 2020;10:1–20.

    Article 

    Google Scholar
     

  • Karabowicz P, Wroński A, Ostrowska H, Waeg G, Zarkovic N, Skrzydlewska E. Reduced proteasome activity and enhanced autophagy in blood cells of psoriatic patients. Int J Mol Sci. 2020;21:1–15.

    Article 

    Google Scholar
     

  • Ambrożewicz E, Wójcik P, Wroński A, Łuczaj W, Jastrząb A, Żarković N, et al. Pathophysiological alterations of redox signaling and endocannabinoid system in granulocytes and plasma of psoriatic patients. Cells. 2018;7:1–18.

    Article 

    Google Scholar
     

  • Kadam DP, Suryakar AN, Ankush RD, Kadam CY, Deshpande KH. Role of oxidative stress in various stages of psoriasis. Indian J Clin Biochem. 2010;25:388–92.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li B, Hao J, Zeng J, Sauter ER. SnapShot: FABP functions. Cell. 2020;182:1066.e1.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Furuhashi M, Hotamisligil GS. Fatty acid-binding proteins: Role in metabolic diseases and potential as drug targets. Nat Rev Drug Discov. 2008;7:489–503.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hao J, Yu J, Yorek MS, Yu CL, Pope RM, Chimenti MS, et al. Keratinocyte FABP5-VCP complex mediates recruitment of neutrophils in psoriasis. Cell Rep. 2023;42:113449.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Peng H, Xin S, Pfeiffer S, Müller C, Merl PJ, Hauck SM, et al. Fatty acid-binding protein 5 is a functional biomarker and indicator of ferroptosis in cerebral hypoxia. Cell Death Dis. 2024;15:1–12.

  • Shou Y, Yang L, Yang Y, Xu J. Inhibition of keratinocyte ferroptosis suppresses psoriatic inflammation. Cell Death Dis. 2021;12:1–10.

    Article 

    Google Scholar
     

  • Vats K, Tian H, Singh K, Tyurina YY, Sparvero LJ, Tyurin VA, et al. Ferroptosis of select skin epithelial cells initiates and maintains chronic systemic immune-mediated psoriatic disease. J Clin Investig. 2024;135:1–16.

  • Romanowska M, Reilly L, Palmer CNA, Gustafsson MCU & Foerster J. Activation of PPARβ/δ causes a psoriasis-like skin disease in vivo. PLoS ONE. 2010;5. e9701:1–14

  • Sano S, Chan KS, Carbajal S, Clifford J, Peavey M, Kiguchi K, et al. Stat3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model. Nat Med. 2005;11:43–49.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wang M, Zhang S, Zheng G, Huang J, Songyang Z, Zhao X, et al. Gain-of-function mutation of card14 leads to spontaneous psoriasis-like skin inflammation through enhanced keratinocyte response to IL-17A. Immunity. 2018;49:66–79.e5.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Manils J, Webb LV, Howes A, Janzen J, Boeing S, Bowcock AM, et al. Card14e138a signalling in keratinocytes induces TNF-dependent skin and systemic inflammation. Elife. 2020;9:1–32.

    Article 

    Google Scholar
     

  • Zenz R, Eferl R, Kenner L, Florin L, Hummerich L, Mehic D, et al. Psoriasis-like skin disease and arthritis caused by inducible epidermal deletion of Jun proteins. Nature. 2005;437:369–75.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Mellett M, Meier B, Mohanan D, Schairer R, Cheng P, Satoh TK, et al. CARD14 Gain-of-function mutation alone is sufficient to drive IL-23/IL-17–mediated psoriasiform skin inflammation in vivo. J Investig Dermatol. 2018;138:2010–23.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chen L, Deshpande M, Grisotto M, Smaldini P, Garcia R, He Z, et al. Skin expression of IL-23 drives the development of psoriasis and psoriatic arthritis in mice. Sci Rep. 2020;10:4–14.


    Google Scholar
     

  • Gago LN, Mellor LF, Megías D, Martín SG, Izeta A, Jimenez F, et al. Role of bulge epidermal stem cells and TSLP signaling in psoriasis. EMBO Mol Med. 2019;11:1–21.


    Google Scholar
     

  • Mellor LF, Gago LN, Bakiri L, Schmidt FN, Busse B, Rauber S, et al. Keratinocyte-derived S100A9 modulates neutrophil infiltration and affects psoriasis-like skin and joint disease. Ann Rheum Dis. 2022;81:1400–8.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Schonthaler HB, Guinea-Viniegra J, Wculek SK, Ruppen I, Ximénez EP, Guío CA, et al. S100A8-S100A9 protein complex mediates psoriasis by regulating the expression of complement factor C3. Immunity. 2013;39:1171–81.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Schonthaler HB, Huggenberger R, Wculek SK, Detmar M, Wagner EF. Systemic anti-VEGF treatment strongly reduces skin inflammation in a mouse model of psoriasis. Proc Natl Acad Sci USA. 2009;106:21264–9.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Glitzner E, Korosec A, Brunner PM, Drobits B, Amberg N, Schonthaler HB, et al. Specific roles for dendritic cell subsets during initiation and progression of psoriasis. EMBO Mol Med. 2014;6:1312–27.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kozłowska D, Myśliwiec H, Harasim-Symbor E, Milewska AJ, Chabowski A, Flisiak I. Serum fatty acid binding protein 5 (FABP5) as a potential biomarker of inflammation in psoriasis. Mol Biol Rep. 2021;48:4421–9.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Berger WT, Ralph BP, Kaczocha M, Sun J, Balius TE, Rizzo RC, et al. Targeting fatty acid binding protein (FABP) anandamide transporters—a novel strategy for development of anti-inflammatory and anti-nociceptive drugs. PLoS ONE. 2012;7:e50968.

  • Kaczocha M, Rebecchi MJ, Ralph BP, Teng  YG, Berger WT, Galbavy W et al. Inhibition of fatty acid binding proteins elevates brain anandamide levels and produces analgesia. PLoS ONE. 2014;9:1–10.

    Article 

    Google Scholar
     

  • Liu J, Chang HW, Grewal R, Cummins DD, Bui A, Beck KM, et al. Transcriptomic profiling of plaque psoriasis and cutaneous T-cell subsets during treatment with secukinumab. JID Innov. 2022;2:100094.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zilka O, Shah R, Li B, Friedmann Angeli JP, Griesser M, Conrad M, et al. On the mechanism of cytoprotection by ferrostatin-1 and liproxstatin-1 and the role of lipid peroxidation in ferroptotic cell death. ACS Cent Sci. 2017;3:232–43.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Furue K, Ito T, Furue M. Differential efficacy of biologic treatments targeting the TNF-α/IL-23/IL-17 axis in psoriasis and psoriatic arthritis. Cytokine. 2018;111:182–8.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Boutet MA, Nerviani A, Gallo Afflitto G, Pitzalis C. Role of the IL-23/IL-17 axis in psoriasis and psoriatic arthritis: the clinical importance of its divergence in skin and joints. Int J Mol Sci. 2018;19:1–27.

  • Al-Janabi A, Yiu Z. Biologics in psoriasis: updated perspectives on long-term safety and risk management [corrigendum]. Psoriasis Targets Ther. 2022;12:187–8.

    Article 

    Google Scholar
     

  • Xu C, Sun S, Johnson T, Qi R, Zhang S, Zhang J, et al. The glutathione peroxidase Gpx4 prevents lipid peroxidation and ferroptosis to sustain Treg cell activation and suppression of antitumor immunity. Cell Rep. 2021;35:109235.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Jin R, Hao J, Yu J, Wang P, Sauter ER, Li B. Role of FABP5 in T cell lipid metabolism and function in the tumor microenvironment. Cancers. 2023;15:1–15.

  • Yang X, Liu Y, Wang Z, Jin Y, Gu W. Ferroptosis as a new tool for tumor suppression through lipid peroxidation. Commun Biol. 2024;7:1475.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Takahashi N, Cho P, Selfors LM, Kuiken HJ, Kaul R, Fujiwara T, et al. 3D Culture models with CRISPR screens reveal hyperactive NRF2 as a prerequisite for spheroid formation via regulation of proliferation and ferroptosis. Mol Cell. 2020;80:828–844.e6.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jimenez R, Toral M, Gómez-Guzmán M, Romero M, Sanchez M, Mahmoud AM, et al. The role of Nrf2 signaling in PPARβ/δ-mediated vascular protection against hyperglycemia-induced oxidative stress. Oxid Med Cell Longev. 2018;2018:1–12.

  • Mieczkowski K, Bakiri L, Griss J & Wagner EF. A sex-specific anti-inflammatory role for p62 in psoriasis-like disease. J Investig Dermatol. 2025;145:2763–2774.e11.

  • Miyake T, Ogawa E, Mikoshiba A, Kobayashi A, Hosoe H, Kashiwabara S, et al. Epidermal-type FABP is a predictive marker of clinical response to systemic treatment and ultraviolet therapy in psoriatic skin lesions. J Dermatol Sci. 2012;68:199–202.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yan B, Liu P, Yi X, Li J, Liu N, Zhu W, et al. Topical VX-509 attenuates psoriatic inflammation through the STAT3/FABP5 pathway in keratinocytes. Pharmacol Res. 2022;182:106318.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Swindell WR, Michaels KA, Sutter AJ, Diaconu D, Fritz Y, Xing X, et al. Imiquimod has strain-dependent effects in mice and does not uniquely model human psoriasis. Genome Med. 2017;9:1–21.

    Article 

    Google Scholar
     

  • Vinardell MP. Methodological shortcomings in the reports of the imiquimod psoriatic model. Exp Dermatol. 2022;31:299–303.

    Article 
    PubMed 

    Google Scholar
     

  • Sengupta A, Lichti UF, Carlson BA, Cataisson C, Ryscavage AO, Mikulec C, et al. Targeted disruption of glutathione peroxidase 4 in mouse skin epithelial cells impairs postnatal hair follicle morphogenesis that is partially rescued through inhibition of COX-2. J Investig Dermatol. 2013;133:1731–41.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hotamisligil GS, Bernlohr DA. Metabolic functions of FABPs – Mechanisms and therapeutic implications. Nat Rev Endocrinol. 2015;11:592–605.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kim DJ, Bility MT, Billin AN, Willson TM, Gonzalez FJ, Peters JM. PPARβ/δ selectively induces differentiation and inhibits cell proliferation. Cell Death Differ. 2006;13:53–60.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Blunder S, Pavel P, Minzaghi D, Dubrac S. PPARdelta in affected atopic dermatitis and psoriasis: a possible role in metabolic reprogramming. Int J Mol Sci 2021;22:1–19.

  • Rivier M, Safonova I, Lebrun P, Griffiths CE, Ailhaud G, Michel S. Differential expression of peroxisome proliferator-activated receptor subtypes during the differentiation of human keratinocytes. J Investig Dermatol. 1998;111:1116–21.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chamcheu JC, Chaves-Rodriquez MI, Adhami VM, Siddiqui IA, Wood GS, Longley BJ, et al. Upregulation of PI3K/AKT/mTOR, FABP5 and PPARβ/δ in human psoriasis and imiquimod-induced murine psoriasiform dermatitis model. Acta Derm Venereol. 2016;96:854–6.

    CAS 
    PubMed 

    Google Scholar
     

  • Guo Q, Kawahata I, Cheng A, Wang H, Jia W, Yoshino H, et al. Fatty acid-binding proteins 3 and 5 are involved in the initiation of mitochondrial damage in ischemic neurons. Redox Biol. 2023;59:102547.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Sorokin AV, Domenichiello AF, Dey AK, Yuan ZX, Goyal A, Rose SM, et al. Bioactive lipid mediator profiles in human psoriasis skin and blood. J Investig Dermatol. 2018;138:1518–28.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hammarström S, Hamberg M, Samuelsson B, Duell EA, Stawiski M, Voorhees JJ. Increased concentrations of nonesterified arachidonic acid, 12L hydroxy 5,8,10,14 eicosatetraenoic acid, prostaglandin E2, and prostaglandin F(2α) in epidermis of psoriasis. Proc Natl Acad Sci USA. 1975;72:5130–4.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kamata M, Tada Y. Efficacy and safety of biologics for psoriasis and psoriatic arthritis and their impact on comorbidities: a literature review. Int J Mol Sci. 2020;21:1–12.

    Article 

    Google Scholar
     

  • Ruyssen-Witrand A, Perry R, Watkins C, Braileanu G, Kumar G, Kiri S, et al. Efficacy and safety of biologics in psoriatic arthritis: a systematic literature review and network meta-analysis. BMJ Open Sport Exerc Med. 2020;6:1–12.


    Google Scholar
     

  • Xu S, Gao X, Deng J, Yang J, Pan F. Comparative efficacy and safety of biologics in moderate to severe plaque psoriasis: a multiple-treatments meta-analysis. J Dtsch Dermatol Ges. 2021;19:47–56.

    PubMed 

    Google Scholar
     

  • Mease P, van der Heijde D, Landewé R, Mpofu S, Rahman P, Tahir H, et al. Secukinumab improves active psoriatic arthritis symptoms and inhibits radiographic progression: Primary results from the randomised, double-blind, phase III FUTURE 5 study. Ann Rheum Dis. 2018;77:890–7.

    Article 
    CAS 
    PubMed 

    Google Scholar