ABSTRACT:Exchange

No abstract

Membranous glomerulonephropathy (MGN) is a glomerulopathy characterized by subepithelial deposits of immune complexes on the extracapillary side of the glomerular basement membrane. Insertion of C5b‐9 (complement membrane‐attack complex) into the membrane leads to functional impairment of the glomerular capillary wall. Knowledge of the molecular pathogenesis of MGN is actually scanty. MicroRNA (miRNA) profiling in MGN and unaffected tissues was performed by TaqMan Low‐Density Arrays. Expression of miRNAs and miRNA targets was evaluated in Real‐Time polymerase chain reaction (PCR). In vitro transient silencing of miRNAs was achieved through transfection with miRNA inhibitors. Ten miRNAs (let‐7a‐5p, let‐7b‐5p, let‐7c‐5p, let‐7d‐5p, miR‐107, miR‐129‐3p, miR‐423‐5p, miR‐516‐3p, miR‐532‐3p, and miR‐1275) were differentially expressed (DE) in MGN biopsies compared to unaffected controls. Interleukin 6 (IL6) and MYC messenger RNAs (mRNAs; targets of DE miRNAs) were significantly downregulated in biopsies from MGN patients, and upregulated in A498 cells following let‐7a‐5p or let‐7c‐5p transient silencing. Gene ontology analysis showed that DE miRNAs regulate pathways associated with MGN pathogenesis, including cell cycle, proliferation, and apoptosis. A significant correlation between DE miRNAs and mRNAs and clinical parameters (i.e., antiphospholipid antibodies, serum creatinine, estimated glomerular filtration, proteinuria, and serum cholesterol) has been detected. Based on our data, we propose that DE miRNAs and their downstream network may be involved in MGN pathogenesis and could be considered as potential diagnostic biomarkers of MGN.

Cell-mediated immune events play a role in the pathogenesis of myocarditis provoked by Group B coxsackievirus (CVB). Studies indicated the synthetic derivative of androstene-3β,7β,17βtriol, HE3286 (17α-ethynyl-5-androstene-3β,7β,17β-triol), may ameliorate the course of immunoinflammatory and autoimmune diseases in rodents. The aim of this study was to evaluate effects of HE3286 on histological signs of CVB-induced myocarditis. BALB/c mice were infected with coxsackie B3 virus (CB3V) and treated by intraperitoneal administration of dexamethasone (Dex) or by oral gavage with HE3286 or with its vehicle, HERF405, for 18 days. Mice were sacrificed and hearts were explanted for histological and immunohistochemical analysis (TNF-α, IL-6, MMP9, ADAM10 and HSP-70). Heart tissues of Dex-treated mice showed a better histological structure compared with mice treated with HERF405. An almost complete resolution of myocarditis was observed in HE3286-treated mice as evidenced by lack of inflammatory infiltration. Immunohistochemical findings confirmed HE3286 had a more pronounced effect than Dex in reducing inflammatory response associated with in situ modulation of cytokine expression and tissue remodeling. Our data demonstrate HE3286 has better results in inhibiting establishment and progression of murine CVB-induced myocarditis than Dex, suggesting this drug may also have a therapeutic role in treatment of CVB-induced myocarditis.