JAK-STAT信号通路与玫瑰痤疮

doi:10.35541/cjd.20200592

Abstract

Abstract: 【Abstract】 Studies have shown that rosacea is related to inflammatory factors, neurovascular function, micro-ecological environment and other factors. The Janus kinase （JAK）-signal transducer and activator of transcription （STAT） signaling pathway involves a variety of inflammatory cytokines, and plays an important role in cell proliferation, differentiation, apoptosis, angiogenesis and immune regulation. This review summarizes the JAK-STAT signaling pathway and explores its potential role in rosacea.

Key words: Rosacea, Signal pathway, Neovascularization, pathologic, JAK-STAT signal pathway, Inflammatory factors, Antibacterial peptides

Wang Yaling, Xie Hongfu, Li Ji, Wang Ben. JAK-STAT signaling pathway and rosacea[J]. Chinese Journal of Dermatology, 2023, 56(2): 169-172.doi:10.35541/cjd.20200592

References ［41］

［1］	Gallo RL, Granstein RD, Kang S, et al. Standard classification and pathophysiology of rosacea: the 2017 update by the National Rosacea Society Expert Committee［J］. J Am Acad Dermatol, 2018,78（1）:148⁃155. doi: 10.1016/j.jaad.2017.08.037.
［2］	Gether L, Overgaard LK, Egeberg A, et al. Incidence and prevalence of rosacea: a systematic review and meta⁃analysis［J］. Br J Dermatol, 2018,179（2）:282⁃289. doi: 10.1111/bjd.16481.
［3］	Li J, Wang B, Deng Y, et al. Epidemiological features of rosacea in Changsha, China: a population⁃based, cross⁃sectional study［J］. J Dermatol, 2020,47（5）:497⁃502. doi: 10.1111/1346⁃8138. 15301.
［4］	van Zuuren EJ. Rosacea［J］. N Engl J Med, 2017,377（18）:1754⁃1764. doi: 10.1056/NEJMcp1506630.
［5］	Yamasaki K, Di Nardo A, Bardan A, et al. Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea［J］. Nat Med, 2007,13（8）:975⁃980. doi: 10.1038/nm1616.
［6］	Li T, Zeng Q, Chen X, et al. The therapeutic effect of artesunate on rosacea through the inhibition of the JAK/STAT signaling pathway［J］. Mol Med Rep, 2018,17（6）:8385⁃8390. doi: 10.3892/ mmr.2018.8887.
［7］	Recio C, Guerra B, Guerra⁃Rodríguez M, et al. Signal transducer and activator of transcription （STAT）⁃5: an opportunity for drug development in oncohematology［J］. Oncogene, 2019,38（24）:4657⁃4668. doi: 10.1038/s41388⁃019⁃0752⁃3.
［8］	Aaronson DS, Horvath CM. A road map for those who don′t know JAK⁃STAT［J］. Science, 2002,296（5573）:1653⁃1655. doi: 10. 1126/science.1071545.
［9］	Malemud CJ. The role of the JAK/STAT signal pathway in rheumatoid arthritis［J］. Ther Adv Musculoskelet Dis, 2018,10（5⁃6）:117⁃127. doi: 10.1177/1759720X18776224.
［10］	Sayoc⁃Becerra A, Krishnan M, Fan S, et al. The JAK⁃inhibitor tofacitinib rescues human intestinal epithelial cells and colonoids from cytokine⁃induced barrier dysfunction［J］. Inflamm Bowel Dis, 2020,26（3）:407⁃422. doi: 10.1093/ibd/izz266.
［11］	Cordes F, Lenker E, Spille LJ, et al. Tofacitinib reprograms human monocytes of IBD patients and healthy controls toward a more regulatory phenotype［J］. Inflamm Bowel Dis, 2020,26（3）:391⁃406. doi: 10.1093/ibd/izz213.
［12］	Johansen C, Rittig AH, Mose M, et al. STAT2 is involved in the pathogenesis of psoriasis by promoting CXCL11 and CCL5 production by keratinocytes［J/OL］. PLoS One, 2017,12（5）:e0176994［2020⁃06⁃12］. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0176994. doi: 10.1371/journal.pone.0176994.
［13］	Yamasaki K, Kanada K, Macleod DT, et al. TLR2 expression is increased in rosacea and stimulates enhanced serine protease production by keratinocytes［J］. J Invest Dermatol, 2011,131（3）:688⁃697. doi: 10.1038/jid.2010.351.
［14］	Wang L, Luo J, He S. Induction of MMP⁃9 release from human dermal fibroblasts by thrombin: involvement of JAK/STAT3 signaling pathway in MMP⁃9 release［J］. BMC Cell Biol, 2007,8:14. doi: 10.1186/1471⁃2121⁃8⁃14.
［15］	Buhl T, Sulk M, Nowak P, et al. Molecular and morphological characterization of inflammatory infiltrate in rosacea reveals activation of Th1/Th17 pathways［J］. J Invest Dermatol, 2015,135（9）:2198⁃2208. doi: 10.1038/jid.2015.141.
［16］	Gomaa AH, Yaar M, Eyada MM, et al. Lymphangiogenesis and angiogenesis in non⁃phymatousrosacea［J］. J Cutan Pathol, 2007,34（10）:748⁃753. doi: 10.1111/j.1600⁃0560.2006.00695.x.
［17］	Liu YD, Yu L, Ying L, et al. Toll⁃like receptor 2 regulates metabolic reprogramming in gastric cancer via superoxide dismutase 2［J］. Int J Cancer, 2019,144（12）:3056⁃3069. doi: 10. 1002/ijc.32060.
［18］	Park JW, Lee HS, Lim Y, et al. Rhododendron album Blume extract inhibits TNF⁃α/IFN⁃γ⁃induced chemokine production via blockade of NF⁃κB and JAK/STAT activation in human epidermal keratinocytes［J］. Int J Mol Med, 2018,41（6）:3642⁃3652. doi: 10.3892/ijmm.2018.3556.
［19］	You Z, Timilshina M, Jeong BS, et al. BJ⁃2266 ameliorates experimental autoimmune encephalomyelitis through down⁃regulation of the JAK/STAT signaling pathway［J］. Eur J Immunol, 2017,47（9）:1488⁃1500. doi: 10.1002/eji.201646860.
［20］	Bechara R, Antonios D, Azouri H, et al. Nickel sulfate promotes IL⁃17A producing CD4+ T cells by an IL⁃23⁃dependent mechanism regulated by TLR4 and Jak⁃STAT pathways［J］. J Invest Dermatol, 2017,137（10）:2140⁃2148. doi: 10.1016/j.jid. 2017.05.025.
［21］	Barrat FJ, Crow MK, Ivashkiv LB. Interferon target⁃gene expression and epigenomic signatures in health and disease［J］. Nat Immunol, 2019,20（12）:1574⁃1583. doi: 10.1038/s41590⁃019⁃0466⁃2.
［22］	You T, Bi Y, Li J, et al. IL⁃17 induces reactive astrocytes and up⁃regulation of vascular endothelial growth factor （VEGF） through JAK/STAT signaling［J］. Sci Rep, 2017,7:41779. doi: 10.1038/srep41779.
［23］	Wang Y, Yu X, Song H, et al. The STAT⁃ROS cycle extends IFN⁃induced cancer cell apoptosis［J］. Int J Oncol, 2018,52（1）:305⁃313. doi: 10.3892/ijo.2017.4196.
［24］	Bakar O, Demirçay Z, Yuksel M, et al. The effect of azithromycin on reactive oxygen species in rosacea［J］. Clin Exp Dermatol, 2007,32（2）:197⁃200. doi: 10.1111/j.1365⁃2230.2006.02322.x.
［25］	Yamasaki K, Gallo RL. The molecular pathology of rosacea［J］. J Dermatol Sci, 2009,55（2）:77⁃81. doi: 10.1016/j.jdermsci.2009. 04.007.
［26］	Graepel R, Fernandes ES, Aubdool AA, et al. 4⁃Oxo⁃2⁃nonenal （4⁃ONE）: evidence of transient receptor potential ankyrin 1⁃dependent and ⁃independent nociceptive and vasoactive responses in vivo［J］. J Pharmacol Exp Ther, 2011,337（1）:117⁃124. doi: 10.1124/jpet.110.172403.
［27］	Kim M, Kim KE, Jung HY, et al. Recombinant erythroid differentiation regulator 1 inhibits both inflammation and angiogenesis in a mouse model of rosacea［J］. Exp Dermatol, 2015,24（9）:680⁃685. doi: 10.1111/exd.12745.
［28］	Chompunud Na Ayudhya C, Roy S, Alkanfari I, et al. Identification of gain and loss of function missense variants in MRGPRX2′s transmembrane and intracellular domains for mast cell activation by substance P［J］. Int J Mol Sci, 2019,20（21）:5247. doi: 10.3390/ijms20215247.
［29］	Kohara H, Tajima S, Yamamoto M, et al. Angiogenesis induced by controlled release of neuropeptide substance P［J］. Biomaterials, 2010,31（33）:8617⁃8625. doi: 10.1016/j.biomaterials. 2010.07.079.
［30］	Delgado M, Ganea D. Inhibition of IFN⁃gamma⁃induced janus kinase⁃1⁃STAT1 activation in macrophages by vasoactive intestinal peptide and pituitary adenylatecyclase⁃activating polypeptide［J］. J Immunol, 2000,165（6）:3051⁃3057. doi: 10. 4049/jimmunol.165.6.3051.
［31］	Sędzikowska A, Osęka M, Skopiński P. The impact of age, sex, blepharitis, rosacea and rheumatoid arthritis on Demodex mite infection［J］. Arch Med Sci, 2018,14（2）:353⁃356. doi: 10.5114/aoms.2016.60663.
［32］	Haber R, El Gemayel M. Comorbidities in rosacea: a systematic review and update［J］. J Am Acad Dermatol, 2018,78（4）:786⁃792.e8. doi: 10.1016/j.jaad.2017.09.016.
［33］	Bronte⁃Tinkew DM, Terebiznik M, Franco A, et al. Helicobacter pylori cytotoxin⁃associated gene A activates the signal transducer and activator of transcription 3 pathway in vitro and in vivo［J］. Cancer Res, 2009,69（2）:632⁃639. doi: 10.1158/0008⁃5472.CAN⁃08⁃1191.
［34］	Aloi F, Tomasini C, Soro E, et al. The clinicopathologic spectrum of rhinophyma［J］. J Am Acad Dermatol, 2000,42（3）:468⁃472. doi: 10.1016/s0190⁃9622（00）90220⁃2.
［35］	Maurer B, Distler A, Suliman YA, et al. Vascular endothelial growth factor aggravates fibrosis and vasculopathy in experimental models of systemic sclerosis［J］. Ann Rheum Dis, 2014,73（10）:1880⁃1887. doi: 10.1136/annrheumdis⁃2013⁃203 535.
［36］	Robert S, Gicquel T, Victoni T, et al. Involvement of matrix metalloproteinases （MMPs） and inflammasome pathway in molecular mechanisms of fibrosis［J］. Biosci Rep, 2016,36（4）:e00360. doi: 10.1042/BSR20160107.
［37］	Muto Y, Wang Z, Vanderberghe M, et al. Mast cells are key mediators of cathelicidin⁃initiated skin inflammation in rosacea［J］. J Invest Dermatol, 2014,134（11）:2728⁃2736. doi: 10.1038/jid.2014.222.
［38］	Tellechea A, Leal EC, Kafanas A, et al. Mast cells regulate wound healing in diabetes［J］. Diabetes, 2016,65（7）:2006⁃2019. doi: 10.2337/db15⁃0340.
［39］	Choi JE, Di Nardo A. Skin neurogenic inflammation［J］. Semin Immuno Pathol, 2018,40（3）:249⁃259. doi: 10.1007/s00281⁃018⁃0675⁃z.
［40］	Shelburne CP, McCoy ME, Piekorz R, et al. Stat5: an essential regulator of mast cell biology［J］. Mol Immunol, 2002,38（16⁃18）:1187⁃1191. doi: 10.1016/s0161⁃5890（02）00061⁃5.
［41］	Chakraborty D, Šumová B, Mallano T, et al. Activation of STAT3 integrates common profibrotic pathways to promote fibroblast activation and tissue fibrosis［J］. Nat Commun, 2017,8（1）:1130. doi: 10.1038/s41467⁃017⁃01236⁃6.

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JAK-STAT signaling pathway and rosacea

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