miRNome Expression Analysis Reveals New Players on Leprosy Immune Physiopathology
Leprosy remains as a public health problem and its physiopathology is still not fully understood. MicroRNAs (miRNA) are small RNA non-coding that can interfere with mRNA to regulate gene expression. A few studies using DNA chip microarrays have explored the expression of miRNA in leprosy patients us...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00463/full |
| _version_ | 1818295620257972224 |
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| author | Claudio Guedes Salgado Pablo Pinto Pablo Pinto Raquel Carvalho Bouth Angélica Rita Gobbo Ana Caroline Cunha Messias Tatiana Vinasco Sandoval André Mauricio Ribeiro dos Santos Fabiano Cordeiro Moreira Amanda Ferreira Vidal Luiz Ricardo Goulart Josafá Gonçalves Barreto Josafá Gonçalves Barreto Moisés Batista da Silva Marco Andrey Cipriani Frade John Stewart Spencer Sidney Santos Sidney Santos Ândrea Ribeiro-dos-Santos Ândrea Ribeiro-dos-Santos |
| author_facet | Claudio Guedes Salgado Pablo Pinto Pablo Pinto Raquel Carvalho Bouth Angélica Rita Gobbo Ana Caroline Cunha Messias Tatiana Vinasco Sandoval André Mauricio Ribeiro dos Santos Fabiano Cordeiro Moreira Amanda Ferreira Vidal Luiz Ricardo Goulart Josafá Gonçalves Barreto Josafá Gonçalves Barreto Moisés Batista da Silva Marco Andrey Cipriani Frade John Stewart Spencer Sidney Santos Sidney Santos Ândrea Ribeiro-dos-Santos Ândrea Ribeiro-dos-Santos |
| author_sort | Claudio Guedes Salgado |
| collection | DOAJ |
| description | Leprosy remains as a public health problem and its physiopathology is still not fully understood. MicroRNAs (miRNA) are small RNA non-coding that can interfere with mRNA to regulate gene expression. A few studies using DNA chip microarrays have explored the expression of miRNA in leprosy patients using a predetermined set of genes as targets, providing interesting findings regarding the regulation of immune genes. However, using a predetermined set of genes restricted the possibility of finding new miRNAs that might be involved in different mechanisms of disease. Thus, we examined the miRNome of tuberculoid (TT) and lepromatous (LL) patients using both blood and lesional biopsies from classical leprosy patients (LP) who visited the Dr. Marcello Candia Reference Unit in Sanitary Dermatology in the State of Pará and compared them with healthy subjects. Using a set of tools to correlate significantly differentially expressed miRNAs with their gene targets, we identified possible interactions and networks of miRNAs that might be involved in leprosy immunophysiopathology. Using this approach, we showed that the leprosy miRNA profile in blood is distinct from that in lesional skin as well as that four main groups of genes are the targets of leprosy miRNA: (1) recognition and phagocytosis, with activation of immune effector cells, where the immunosuppressant profile of LL and immunoresponsive profile of TT are clearly affected by miRNA expression; (2) apoptosis, with supportive data for an antiapoptotic leprosy profile based on BCL2, MCL1, and CASP8 expression; (3) Schwann cells (SCs), demyelination and epithelial–mesenchymal transition (EMT), supporting a role for different developmental or differentiation gene families, such as Sox, Zeb, and Hox; and (4) loss of sensation and neuropathic pain, revealing that RHOA, ROCK1, SIGMAR1, and aquaporin-1 (AQP1) may be involved in the loss of sensation or leprosy pain, indicating possible new therapeutic targets. Additionally, AQP1 may also be involved in skin dryness and loss of elasticity, which are well known signs of leprosy but with unrecognized physiopathology. In sum, miRNA expression reveals new aspects of leprosy immunophysiopathology, especially on the regulation of the immune system, apoptosis, SC demyelination, EMT, and neuropathic pain. |
| first_indexed | 2024-12-13T03:50:32Z |
| format | Article |
| id | doaj.art-51330964b24442c7ba93024242a7b8f7 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-13T03:50:32Z |
| publishDate | 2018-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-51330964b24442c7ba93024242a7b8f72022-12-22T00:00:43ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-03-01910.3389/fimmu.2018.00463334762miRNome Expression Analysis Reveals New Players on Leprosy Immune PhysiopathologyClaudio Guedes Salgado0Pablo Pinto1Pablo Pinto2Raquel Carvalho Bouth3Angélica Rita Gobbo4Ana Caroline Cunha Messias5Tatiana Vinasco Sandoval6André Mauricio Ribeiro dos Santos7Fabiano Cordeiro Moreira8Amanda Ferreira Vidal9Luiz Ricardo Goulart10Josafá Gonçalves Barreto11Josafá Gonçalves Barreto12Moisés Batista da Silva13Marco Andrey Cipriani Frade14John Stewart Spencer15Sidney Santos16Sidney Santos17Ândrea Ribeiro-dos-Santos18Ândrea Ribeiro-dos-Santos19Laboratório de Dermato-Imunologia, Instituto de Ciências Biológicas (ICB), Universidade Federal do Pará (UFPA), Marituba, BrazilLaboratório de Genética Humana e Médica, ICB, UFPA, Belém, BrazilNúcleo de Pesquisas em Oncologia (NPO), UFPA, Belém, BrazilLaboratório de Dermato-Imunologia, Instituto de Ciências Biológicas (ICB), Universidade Federal do Pará (UFPA), Marituba, BrazilLaboratório de Dermato-Imunologia, Instituto de Ciências Biológicas (ICB), Universidade Federal do Pará (UFPA), Marituba, BrazilLaboratório de Dermato-Imunologia, Instituto de Ciências Biológicas (ICB), Universidade Federal do Pará (UFPA), Marituba, BrazilLaboratório de Genética Humana e Médica, ICB, UFPA, Belém, BrazilLaboratório de Genética Humana e Médica, ICB, UFPA, Belém, BrazilNúcleo de Pesquisas em Oncologia (NPO), UFPA, Belém, BrazilLaboratório de Genética Humana e Médica, ICB, UFPA, Belém, BrazilLaboratório de Nanobiotecnologia, Instituto de Genética e Bioquímica, Universidade Federal de Uberlândia (UFU), Uberlândia, BrazilLaboratório de Dermato-Imunologia, Instituto de Ciências Biológicas (ICB), Universidade Federal do Pará (UFPA), Marituba, BrazilLaboratório de Epidemiologia Espacial (LabEE), Campus Castanhal, UFPA, Belém, BrazilLaboratório de Dermato-Imunologia, Instituto de Ciências Biológicas (ICB), Universidade Federal do Pará (UFPA), Marituba, BrazilDivisão de Dermatologia, Departamento de Clínica Médica da Faculdade de Medicina de Ribeirão Preto, USP, Ribeirão Preto, BrazilMycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, United StatesLaboratório de Genética Humana e Médica, ICB, UFPA, Belém, BrazilNúcleo de Pesquisas em Oncologia (NPO), UFPA, Belém, BrazilLaboratório de Genética Humana e Médica, ICB, UFPA, Belém, BrazilNúcleo de Pesquisas em Oncologia (NPO), UFPA, Belém, BrazilLeprosy remains as a public health problem and its physiopathology is still not fully understood. MicroRNAs (miRNA) are small RNA non-coding that can interfere with mRNA to regulate gene expression. A few studies using DNA chip microarrays have explored the expression of miRNA in leprosy patients using a predetermined set of genes as targets, providing interesting findings regarding the regulation of immune genes. However, using a predetermined set of genes restricted the possibility of finding new miRNAs that might be involved in different mechanisms of disease. Thus, we examined the miRNome of tuberculoid (TT) and lepromatous (LL) patients using both blood and lesional biopsies from classical leprosy patients (LP) who visited the Dr. Marcello Candia Reference Unit in Sanitary Dermatology in the State of Pará and compared them with healthy subjects. Using a set of tools to correlate significantly differentially expressed miRNAs with their gene targets, we identified possible interactions and networks of miRNAs that might be involved in leprosy immunophysiopathology. Using this approach, we showed that the leprosy miRNA profile in blood is distinct from that in lesional skin as well as that four main groups of genes are the targets of leprosy miRNA: (1) recognition and phagocytosis, with activation of immune effector cells, where the immunosuppressant profile of LL and immunoresponsive profile of TT are clearly affected by miRNA expression; (2) apoptosis, with supportive data for an antiapoptotic leprosy profile based on BCL2, MCL1, and CASP8 expression; (3) Schwann cells (SCs), demyelination and epithelial–mesenchymal transition (EMT), supporting a role for different developmental or differentiation gene families, such as Sox, Zeb, and Hox; and (4) loss of sensation and neuropathic pain, revealing that RHOA, ROCK1, SIGMAR1, and aquaporin-1 (AQP1) may be involved in the loss of sensation or leprosy pain, indicating possible new therapeutic targets. Additionally, AQP1 may also be involved in skin dryness and loss of elasticity, which are well known signs of leprosy but with unrecognized physiopathology. In sum, miRNA expression reveals new aspects of leprosy immunophysiopathology, especially on the regulation of the immune system, apoptosis, SC demyelination, EMT, and neuropathic pain.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00463/fullleprosyimmunologySchwann cellsapoptosisneuropathic painmicroRNA |
| spellingShingle | Claudio Guedes Salgado Pablo Pinto Pablo Pinto Raquel Carvalho Bouth Angélica Rita Gobbo Ana Caroline Cunha Messias Tatiana Vinasco Sandoval André Mauricio Ribeiro dos Santos Fabiano Cordeiro Moreira Amanda Ferreira Vidal Luiz Ricardo Goulart Josafá Gonçalves Barreto Josafá Gonçalves Barreto Moisés Batista da Silva Marco Andrey Cipriani Frade John Stewart Spencer Sidney Santos Sidney Santos Ândrea Ribeiro-dos-Santos Ândrea Ribeiro-dos-Santos miRNome Expression Analysis Reveals New Players on Leprosy Immune Physiopathology Frontiers in Immunology leprosy immunology Schwann cells apoptosis neuropathic pain microRNA |
| title | miRNome Expression Analysis Reveals New Players on Leprosy Immune Physiopathology |
| title_full | miRNome Expression Analysis Reveals New Players on Leprosy Immune Physiopathology |
| title_fullStr | miRNome Expression Analysis Reveals New Players on Leprosy Immune Physiopathology |
| title_full_unstemmed | miRNome Expression Analysis Reveals New Players on Leprosy Immune Physiopathology |
| title_short | miRNome Expression Analysis Reveals New Players on Leprosy Immune Physiopathology |
| title_sort | mirnome expression analysis reveals new players on leprosy immune physiopathology |
| topic | leprosy immunology Schwann cells apoptosis neuropathic pain microRNA |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00463/full |
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