Abstract
TOB/BTG is a family of antiproliferative proteins that play an important role in the regulation of immune responses, acting as lymphocyte activators and macrophage-mediated cytotoxicity. No previous studies have explored their role in patients with psoriasis. The aim of this study was to characterize the expression of TOB/BTG family and their co-localization in skin from patients with psoriasis. This is an exploratory, observational, and cross-sectional study that included 24 plaque psoriasis patients and 15 controls. Gene expression of TOB/BTG family was determinate by RT-PCR. Protein products of TOB/BTG were evaluated by immunohistochemistry and compared with control skin tissues. Holm-Sidak’s multiple comparisons test was performed. TOB/BTG family mRNA levels and protein expression were significantly decreased in psoriatic skin tissue compared to non-inflammatory control skin tissue. Double-positive cell TOB1/2, BTG1,2 and BTG4/CD16 expressions were found in normal control skin tissues through epidermis and dermis (p < 0.001) and lesser percentage in patients with mild, almost absent in moderate-severe plaque psoriasis. This is the first report of the TOB/BTG family gene and protein expression in skin tissues by a CD16 + subpopulation in plaque psoriasis. TOB/BTG family protein might represent a new therapeutic target among immune-mediated inflammatory diseases.
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References
Chen Y, et al. BTG/Tob family members Tob1 and Tob2 inhibit proliferation of mouse embryonic stem cells via Id3 mRNA degradation. Biochem Biophys Res Commun. 2015;462(3):208–14. https://doi.org/10.1016/j.bbrc.2015.04.117.
Sebastiaan G. The mammalian anti-proliferative BTG/Tob protein family. J Cell Physiol. 2010;222(1):66–72. https://doi.org/10.1002/jcp.21919.
Mauxion F, et al. BTG/TOB factors impact deadenylases. Trends Biochem Sci. 2009;34(12):640–7. https://doi.org/10.1016/j.tibs.2009.07.008.
Kawakubo H, et al. Loss of B-cell translocation gene-2 in estrogen receptor-positive breast carcinoma is associated with tumor grade and overexpression of cyclin d1 protein. Cancer Res. 2006;66(14):7075–82. https://doi.org/10.1158/0008-5472.CAN-06-0379.
Iwanaga K, et al. Alteration of expression or phosphorylation status of tob, a novel tumor suppressor gene product, is an early event in lung cancer. Cancer Lett. 2003;202(1):71–9. https://doi.org/10.1016/j.canlet.2003.08.019.
Park GT, et al. TOB is a potential marker gene for the basal layer of the epidermis and is stably expressed in human primary keratinocytes. Br J Dermatol. 2006;154(3):411–8. https://doi.org/10.1111/j.1365-2133.2005.07037.x.
Fonseca-Camarillo G, et al. Expression of TOB/BTG family members in patients with inflammatory bowel disease. Scand J Immunol. 2021;93(4):e13004. https://doi.org/10.1111/sji.13004.
Fonseca-Camarillo G, et al. AKAP12/Gravin is over-expressed in patients with ulcerative colitis. Immunol Res. 2021;69(5):429–35. https://doi.org/10.1007/s12026-021-09214-3.
Toro-Monjaraz EM, et al. Differential cytokine expression in the duodenum and rectum of children with non-immunoglobulin E-mediated cow’s milk protein allergy. Dig Dis Sci. 2021;66(11):3769–75. https://doi.org/10.1007/s10620-020-06743-z.
Fonseca-Camarillo G, et al. Intestinal production of secreted protein acidic and rich in cysteine (SPARC) in patients with ulcerative colitis. Immunobiology. 2021;226(3):152095. https://doi.org/10.1016/j.imbio.2021.152095.
Rendon A, Schäkel K. Psoriasis pathogenesis and treatment. Int J Mol Sci. 2019;20(6):1475. https://doi.org/10.3390/ijms20061475.
Greb JE, et al. Psoriasis. Nature reviews. Dis Prim. 2016;2:16082. https://doi.org/10.1038/nrdp.2016.82.
Matsuda S, et al. In search of a function for the TIS21/PC3/BTG1/TOB family. FEBS Lett. 2001;497(2–3):67–72. https://doi.org/10.1016/s0014-5793(01)02436-x.
Bai Y, et al. Expression and prognosis analyses of the Tob/BTG antiproliferative (APRO) protein family in human cancers. PloS One. 2017;12(9):e0184902. https://doi.org/10.1371/journal.pone.0184902.
Konrad MAP, Zúñiga-Pflücker JC. The BTG/TOB family protein TIS21 regulates stage-specific proliferation of developing thymocytes. Eur J Immunol. 2005;35(10):3030–42. https://doi.org/10.1002/eji.200526345.
Jiang G, et al. Tob2 inhibits TLR-induced inflammatory responses by association with TRAF6 and MyD88. J Immunol (Baltimore, Md : 1950). 2020;205(4):981–6. https://doi.org/10.4049/jimmunol.2000057.
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This work was supported by funds from the Inflammatory Bowel Disease Clinic at the Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”.
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Barrera-Ochoa Carlos A. and Fonseca-Camarillo Gabriela contributed equally to this work.
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Barrera-Ochoa, C.A., Fonseca-Camarillo, G., Vega-Memije, M.E. et al. Differential expression of TOB/BTG family members in patients with plaque psoriasis: cross-sectional study. Immunol Res 72, 234–241 (2024). https://doi.org/10.1007/s12026-023-09427-8
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DOI: https://doi.org/10.1007/s12026-023-09427-8