Background and Purpose Inflammatory processes induced by leukocytes are crucially involved in the pathophysiology of acute ischemic stroke. This study aimed to elucidate the inflammatory mechanism of long non-coding RNA (lncRNA) H19-mediated regulation of C1QTNF6 by sponging miR-29b in leukocytes during ischemic stroke. Experimental Approach H19 and miR-29b expression in leukocytes of patients with ischemic stroke and middle cerebral artery occlusion rats was measured through real-time PCR. Moreover, we performed in vivo and in vitro experiments to determine the impact of H19 and miR-29b on C1QTNF6 expression in leukocytes after ischemic injury. Key Results There was H19 and C1QTNF6 upregulation, as well as miR-29b downregulation, in neutrophils of patients with stroke. Moreover, miR-29b could bind C1QTNF6 mRNA to repress its expression while H19 could sponge miR-29b to maintain C1QTNF6 expression. Moreover, C1QTNF6 overexpression promoted the release of IL-1β and TNF-α in leukocytes and further exacerbates blood-brain barrier disruption. Conclusion and Implications Our findings confirm the inflammation-modulatory effect of the H19/miR-29b/C1QTNF6 axis on cerebral ischemic injury.

EPO has been found to be protective to multiple injuries long time ago. Discovery of the so-called tissue protective receptor “EPOR/βcR” is astonishing among EPO researchers. βcR is a receptor subunit shared by IL-3/IL-5/GM-CSF and EPO, but no attention has been paid to these three cytokines in EPO research. This article unprecedentedly presented that potential relations between EPO and IL-3/IL-5/GM-CSF should be highly valued. We respectively compared GM-CSF and IL-3 to EPO/EPO derivatives, and summarized similar and opposite functions between these two cytokines and EPO/EPO derivatives. Here, drawbacks of the EPOR/βcR theory were deeply discussed and new hypothesis about the mechanism of EPO protection was proposed. In a word, referring to stagnation of EPO research and defects of current recognition, reassessment of our understandings about EPO’s protective function is of great urgency.