A Description of the Hemolytic Component in Sickle Leg Ulcer: The Role of Circulating miR-199a-5p, miR-144, and miR-126

Biomolecules

Idaiara Graziele Silva Quadros¹  Teresa Cristina Cardoso Fonseca²  Marilda Souza Goncalves³  Rayra Pereira Santiago³  Caroline Conceição da Guarda³  Luciana Magalhães Fiuza³  Suéllen Pinheiro Carvalho³  Sètondji Cocou Modeste Alexandre Yahouédéhou³  Paulo Vinícius Bispo Santana⁴  Edvan do Carmo Santos⁴  Carla Martins Kaneto⁴  Gabriela Imbassahy Valentim Melo⁴  Milena Magalhães Aleluia⁴  Elisângela Vitória Adorno⁵ 

[1] Centro de Referência a Doença Falciforme de Itabuna, Itabuna 45600-075, BA, Brazil;Departamento de Ciências da Saúde, Universidade Estadual de Santa Cruz, Ilhéus 45662-900, BA, Brazil;Laboratório de Investigação em Genética e Hematologia Translacional, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador 40296-710, BA, Brazil;Laboratório de Patologia Aplicada e Genética, Departamento de Ciências Biológicas, Universidade Estadual de Santa Cruz, Ilhéus 45662-900, BA, Brazil;Laboratório de Pesquisa em Anemias, Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal da Bahia, Salvador 40170-115, BA, Brazil;

关键词: sickle cell disease;    sickle leg ulcer;    microRNA;    hemolysis;    biomarkers;   

DOI  :  10.3390/biom12020317

来源: DOAJ

【 摘 要 】

Sickle leg ulcers (SLU) are malleoli lesions with exuberant hemolytic pathophysiology. The microRNAs are potential genetic biomarkers for several pathologies. Thereby, we aimed to assess the expression of circulating miR-199a-5p, miR-144, and miR-126 in association with hemolytic biomarkers in SLU. This cross-sectional study included 69 patients with sickle cell disease, 52 patients without SLU (SLU-) and 17 patients with active SLU or previous history (SLU+). The results demonstrated elevated expression of circulating miR-199a-5p and miR-144 in SLU+ patients while miR-126 expression was reduced. Circulating miR-199a-5p and miR-144 were associated with hemolytic biomarkers such as LDH, indirect bilirubin, AST, GGT, iron, ferritin, RBC, hemoglobin, and NOm, in addition to association with impaired clinical profile of SLU. Furthermore, in silico analyses indicated interactions of miR-199a-5p with HIF1A, Ets-1, and TGFB2 genes, which are associated with vasculopathy and reduced NO. In contrast, miR-126 was associated with an attenuating clinical profile of SLU, in addition to not characterizing hemolysis. In summary, this study demonstrates, for the first time, that hemolytic mechanism in SLU can be characterized by circulating miR-199a-5p and miR-144. The circulating miR-126 may play a protective role in SLU. Thus, these microRNAs can support to establish prognosis and therapeutic strategy in SLU.

【 授权许可】

Unknown