Increased matrix metalloproteinases expression in tuberous sclerosis complex: modulation by microRNA 146a and 147b in vitro

摘要: Aim: Matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs) control proteolysis within the extracellular matrix (ECM) of brain. Dysfunction this enzymatic system due to brain inflammation can disrupt blood-brain barrier (BBB) has been implicated in pathogenesis epilepsy. However, not extensively studied epileptogenic human Methods: We investigated expression cellular localization major MMPs (MMP2, MMP3, MMP9 MMP14) TIMPs (TIMP1, TIMP2, TIMP3 TIMP4) using quantitative real-time polymerase chain reaction (RT-PCR) immunohistochemistry resected from patients with tuberous sclerosis complex (TSC), a severe neurodevelopmental disorder characterized by intractable epilepsy prominent neuroinflammation. Furthermore, we determined whether anti-inflammatory microRNAs, miR146a miR147b, which regulate gene at transcriptional level, could attenuate dysregulated MMP TIMP TSC tuber-derived astroglial cultures. Results: demonstrated higher mRNA protein tubers compared perituberal tissue, particularly dysmorphic neurons giant cells, as well reactive astrocytes, was associated BBB dysfunction. More importantly, IL-1β-induced dysregulation TIMP4 be rescued miR147b Conclusions: This study provides evidence MMP/TIMP proteolytic TSC, is As ameliorated vitro these miRNAs deserve further investigation novel therapeutic approach.