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Inhibition of miR-103-3p Preserves Neurovascular Integrity Through Caveolin-1 in Experimental Subarachnoid Hemorrhage

2021; Elsevier BV; Volume: 461; Linguagem: Inglês

10.1016/j.neuroscience.2021.03.007

1873-7544

Liumin Wang, Ying Zhao, Shucheng Gang, Tongchao Geng, Mingquan Li, Lili Xu, Xiaohao Zhang, Ling Liu, Yi Xie, Ruidong Ye, Xinfeng Liu,

Intracerebral and Subarachnoid Hemorrhage Research

Caveolin-1 (Cav-1) is a constitutive structural protein of caveolae in the plasma membrane. It plays an important role in maintaining blood brain barrier (BBB) integrity. In this study, we identified that miR-103-3p, a hypoxia-responsive miRNA, could interact with Cav-1. In endothelial cells, miR-103-3p mimic diminished the expression of Cav-1 and tight junction proteins, which were rescued by the inhibition of miR-103-3p. We found a substantial increase of miR-103-3p and decease of Cav-1 in the rat subarachnoid hemorrhage (SAH) model. Pre-SAH intracerebroventricularly injection of miR-103-3p antagomir relieved Cav-1 loss, sequentially reduced BBB permeability and improved neurological function. Finally, we demonstrated that the salutary effects of miR-103-3p antagomir were abolished in Cav-1 knock-out mice, suggesting that Cav-1 was required for the miR-103-3p inhibition-induced neurovascular protection. Taken together, our findings suggest that the inhibition of miR-103-3p could exert neuroprotective effects through preservation of Cav-1 and BBB integrity, making miR-103-3p a novel therapeutic target for SAH.