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Association between histopathological changes and expression of selected microRNAs in skin of adult patients with IgA vasculitis
Author(s) -
Jurčić Vesna,
Bolha Luka,
Matjašič Alenka,
Sedej Ivana,
Dolinar Ana,
Grubelnik Gašper,
Hauptman Nina,
Pižem Jože,
Jevšinek-Skok Daša,
Hočevar Alojzija,
RavnikGlavač Metka,
Glavač Damjan
Publication year - 2019
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13927
Subject(s) - pathology , microrna , fibrinoid necrosis , infiltration (hvac) , proinflammatory cytokine , necrosis , vasculitis , biology , medicine , inflammation , immunology , gene , biochemistry , physics , disease , thermodynamics
Aims IgA vasculitis (IgAV) is a common small‐vessel systemic vasculitisthat is histologically characterised by granulocyte infiltration and IgA deposition in vessel walls. Information on microRNA (miRNA) involvement inIgAVis limited. The aim of this study was to analyse the association between histopathological changes and expression profiles of 14 miRNAs in the affected skin of 70 adult patients with IgAV. Methods and results miRNA expression analysis was performed by quantitative real‐time polymerase chain reaction and evaluation of histopathological changes by light and immunofluorescence microscopy on formalin‐fixed paraffin‐embedded skin excision samples. In IgAV‐affected skin, granulocyte infiltration was significantly associated with vessel fibrinoid necrosis. Of the analysed miRNAs, four showed two‐fold increased expression (let‐7d, let‐7f, miR‐21‐5p, and miR‐203‐3p), five showed five‐fold increased expression (let‐7b, miR‐17‐5p, miR‐155‐5p, miR‐423‐5p, and miR‐451a), and threeshowed 15‐fold increased expression (let‐7a, miR‐21‐3p, miR‐223‐3p), as compared with controls (all P < 0.001). miR‐146a‐5p and miR‐148b‐3p showed three‐fold decreased expression ( P = 0.981 and P < 0.001). The expression of miR‐223‐3p also showed a significant positive association with granulocyte infiltration and fibrinoid necrosis. Conclusions Altered miRNA expression, especially of miRNA‐223‐3p, may be associated with the skin inflammatory state in IgAV. The majority of aberrantly expressed miRNAs in IgAV‐affected skin are known to influence the nuclear factor‐κB signalling pathway, which is crucial for activation of key proinflammatory genes, including those encoding tumour necrosis factor‐α, interleukin (IL)‐6, and IL‐8. Furthermore, miR‐146a‐5p and miR‐148b‐3p, which are negative regulators of inflammatory gene expression, showed decreased expression and could contribute to the exaggerated inflammation. Further investigation of miRNA expression in the affected tissues could improve our knowledge of IgAV pathogenesis, and possibly help to identify novel biomarkers in body fluids.