Institute of Neuroscience, Soochow University, Suzhou City, China.
College of Forestry, Nanjing Forestry University, Nanjing City, China.
J Cell Mol Med. 2021 Dec;25(24):11300-11309. doi: 10.1111/jcmm.17060. Epub 2021 Nov 19.
βII spectrin (β2SP) is encoded by Sptbn1 and is involved in the regulation of various cell functions. β2SP contributes to the formation of the myelin sheath, which may be related to the mechanism of neuropathy caused by demyelination. As one of the main features of cerebral ischemia, demyelination plays a key role in the mechanism of cerebral ischemia injury. Here, we showed that β2SP levels were increased, and this molecule interacted with TET2 after ischemic injury. Furthermore, we found that the level of TET2 was decreased in the nucleus when β2SP was knocked out after oxygen and glucose deprivation (OGD), and the level of 5hmC was reduced in the OGD+β2SP KO group. In contrast, the expression of β2SP did not change in TET2 KO mice. In addition, the 5hmC sequencing results revealed that β2SP can affect the level of 5hmC, the differentially hydroxymethylated region (DhMR) mainly related with the Calcium signalling pathway, cGMP-PKG signalling pathway, Wnt signalling pathway and Hippo signalling pathway. In summary, our results suggest that β2SP could regulate the gene 5hmC by interacted with TET2 and will become a potential therapeutic target for ischemic stroke.
βII spectrin (β2SP) 由 Sptbn1 编码，参与多种细胞功能的调节。β2SP 有助于髓鞘的形成，这可能与脱髓鞘引起的神经病变机制有关。作为脑缺血的主要特征之一，脱髓鞘在脑缺血损伤机制中起关键作用。在这里，我们发现β2SP 水平升高，并且这种分子在缺血损伤后与 TET2 相互作用。此外，我们发现，在氧葡萄糖剥夺（OGD）后敲除β2SP 时，TET2 的核内水平降低，并且在 OGD+β2SP KO 组中 5hmC 的水平降低。相比之下，在 TET2 KO 小鼠中β2SP 的表达没有变化。此外，5hmC 测序结果表明，β2SP 可以通过与 TET2 相互作用来影响 5hmC 的水平，差异羟甲基化区域（DhMR）主要与钙信号通路、cGMP-PKG 信号通路、Wnt 信号通路和 Hippo 信号通路有关。总之，我们的结果表明，β2SP 可以通过与 TET2 相互作用来调节基因 5hmC，并可能成为缺血性中风的潜在治疗靶点。
