microRNA-130b May Induce Cerebral Vasospasm after Subarachnoid Hemorrhage via Modulating Kruppel-like Factor 4.

Recently, the diverse functions of microRNAs (miRNAs) in brain diseases have been demonstrated. We intended to uncover the functional role of microRNA-130b (miR-130b) in cerebral vasospasm (CVS) following subarachnoid hemorrhage (SAH). SAH was induced by injecting the autologous blood into the cisterna magna of Sprague Dawley rats. The cerebral vascular smooth muscle cells (cVSMCs) were extracted for in vitro experimentation. In vitro and in vivo assays were implemented with transfection of miR-130b mimic/inhibitor, sh-Kruppel-like factor 4 (KLF4), oe-KLF4 plasmids or p38/MAPK signaling pathway agonist (anisomycin), respectively, to elaborate the role of miR-130b in CVS following SAH. Elevated miR-130b and reduced KLF4 were found in SAH patients and rat models of SAH. KLF4 was the target gene of miR-130b. miR-130b promoted the proliferation and migration of cVSMCs through the Inhibition of KLF4. Besides, KLF4 inhibited the proliferation and migration of cVSMCs through blockage of the p38/MAPK pathway. Furthermore, in vivo assay confirmed the inhibitory effect of decreased miR-130b in CVS following SAH. In conclusion, miR-130b may activate the p38/MAPK signaling pathway through targeted inhibition of KLF4, thereby contributing to some extent to the development of cerebral vasospasm after SAH.

Downregulation of miR-26b attenuates early brain injury induced by subarachnoid hemorrhage via mediating the KLF4/STAT3/HMGB1 axis.

BACKGROUND: Early brain injury (EBI) refers to early-onset secondary complications that occur after subarachnoid hemorrhage (SAH), and associated with high rate of disability and mortality. Recent investigations have indicated microRNA-26b (miR-26b) as a biomarker in the progression of SAH. Accordingly, the present study was designed to elucidate the role of miR-26b in influencing EBI following SAH and the downstream mechanisms. METHODS: Firstly, SAH rat models and neuron injury models were developed to assess the effect of miR-26b on EBI-like symptoms and subsequent inflammation. Dual-luciferase reporter gene assay was further implemented to evaluate the binding of miR-26b to its putative target gene STAT3. Loss-of-function and rescue experiments were performed to assess the functionality of miR-26b-mediated STAT3 in both models. RESULTS: miR-26b was found to target KLF4 and negative-modulate its expression, whereby aggravating EBI and inflammatory response in SAH rat models and stimulating hemoglobin-induced apoptosis in astrocytes. On the other hand, silencing of miR-26b reversed these changes in SAH rat models and hemoglobin (Hb)-induced astrocytes. miR-26b could further activate STAT3 via down-regulation of KLF4. Furthermore, KLF4 knockdown up-regulated HMGB1 to aggravate EBI following SAH. CONCLUSIONS: Collectively, our findings highlighted the ameliorative effect of miR-26b inhibition on EBI in SAH and the possible mechanism associated with the KLF4/STAT3/HMGB1 axis.