The LncRNA H19/miR-1-3p/CCL2 axis modulates lipopolysaccharide (LPS) stimulation-induced normal human astrocyte proliferation and activation

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2020-07, Vol.131, p.155106-155106, Article 155106
• Main Authors: Li, Pengzhi, Li, Yawei, Dai, Yuliang, Wang, Bing, Li, Lei, Jiang, Bin, Wu, Pengfei, Xu, Jietao
• Format: Article
• Language: English
• Subjects: CCL2; H19; miR-1-3p; normal human astrocytes (NHAs); spinal cord injury (SCI)
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2020.155106

Reactive astrocyte proliferation post SCI (spinal cord injury) leads to the formation of glial scars, thus hindering axon regeneration and SCI repair, during which the activation of astrocytes plays a central role. This study attempted to identify the lncRNA-miRNA-mRNA network which exerts a critical effect on normal human astrocyte (NHA) activation and proliferation during SCI inflammation. Herein, lncRNA H19 expression was increased by LPS in NHAs, and H19 was positively correlated with CCL2. H19 silencing in NHAs significantly attenuated the promoting effects of LPS stimulation on NHA proliferation and activation as manifested by inhibited cell viability and DNA synthesis capacity, reduced NHA activation markers, and reduced inflammatory factor concentrations (CCL2, IL-6, and TNF-α). miR-1-3p directly bound to H19 and the CCL2 3′UTR. miR-1-3p overexpression also attenuated the promoting effects of LPS stimulation on NHA proliferation and activation. H19 relieved miR-1-3p-induced inhibition of CCL2 expression by acting as a ceRNA. The inhibition of miR-1-3p could significantly reverse the effects of H19 silencing on NHA proliferation and activation, suggesting that the H19/miR-1-3p axis regulates the proliferation and activation of NHAs via CCL2. In conclusion, lncRNA H19, miR-1-3p, and CCL2 form a lncRNA-miRNA-mRNA axis that modulates NHA proliferation and activation in vitro.