| Autor: |
Salgado CG; Laboratório de Dermato-Imunologia, Instituto de Ciências Biológicas (ICB), Universidade Federal do Pará (UFPA), Marituba, Brazil., Pinto P; Laboratório de Genética Humana e Médica, ICB, UFPA, Belém, Brazil.; Núcleo de Pesquisas em Oncologia (NPO), UFPA, Belém, Brazil., Bouth RC; Laboratório de Dermato-Imunologia, Instituto de Ciências Biológicas (ICB), Universidade Federal do Pará (UFPA), Marituba, Brazil., Gobbo AR; Laboratório de Dermato-Imunologia, Instituto de Ciências Biológicas (ICB), Universidade Federal do Pará (UFPA), Marituba, Brazil., Messias ACC; Laboratório de Dermato-Imunologia, Instituto de Ciências Biológicas (ICB), Universidade Federal do Pará (UFPA), Marituba, Brazil., Sandoval TV; Laboratório de Genética Humana e Médica, ICB, UFPA, Belém, Brazil., Dos Santos AMR; Laboratório de Genética Humana e Médica, ICB, UFPA, Belém, Brazil., Moreira FC; Núcleo de Pesquisas em Oncologia (NPO), UFPA, Belém, Brazil., Vidal AF; Laboratório de Genética Humana e Médica, ICB, UFPA, Belém, Brazil., Goulart LR; Laboratório de Nanobiotecnologia, Instituto de Genética e Bioquímica, Universidade Federal de Uberlândia (UFU), Uberlândia, Brazil., Barreto JG; Laboratório de Dermato-Imunologia, Instituto de Ciências Biológicas (ICB), Universidade Federal do Pará (UFPA), Marituba, Brazil.; Laboratório de Epidemiologia Espacial (LabEE), Campus Castanhal, UFPA, Belém, Brazil., da Silva MB; Laboratório de Dermato-Imunologia, Instituto de Ciências Biológicas (ICB), Universidade Federal do Pará (UFPA), Marituba, Brazil., Frade MAC; Divisão de Dermatologia, Departamento de Clínica Médica da Faculdade de Medicina de Ribeirão Preto, USP, Ribeirão Preto, Brazil., Spencer JS; Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, United States., Santos S; Laboratório de Genética Humana e Médica, ICB, UFPA, Belém, Brazil.; Núcleo de Pesquisas em Oncologia (NPO), UFPA, Belém, Brazil., Ribeiro-Dos-Santos Â; Laboratório de Genética Humana e Médica, ICB, UFPA, Belém, Brazil.; Núcleo de Pesquisas em Oncologia (NPO), UFPA, Belém, Brazil. |
| Abstrakt: |
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. |
