Corrigendum: MicroRNA339 Targeting PDXK Improves Motor Dysfunction and Promotes Neurite Growth in the Remote Cortex Subjected to Spinal Cord Transection.

[This corrects the article DOI: 10.3389/fcell.2020.00577.].

MicroRNA339 Targeting PDXK Improves Motor Dysfunction and Promotes Neurite Growth in the Remote Cortex Subjected to Spinal Cord Transection.

Spinal cord injury (SCI) is a fatal disease that can cause severe disability. Cortical reorganization subserved the recovery of spontaneous function after SCI, although the potential molecular mechanism in this remote control is largely unknown. Therefore, using proteomics analysis, RNA interference/overexpression, and CRISPR/Cas9 in vivo and in vitro, we analyzed how the molecular network functions in neurological improvement, especially in the recovery of motor function after spinal cord transection (SCT) via the remote regulation of cerebral cortex. We discovered that the overexpression of pyridoxal kinase (PDXK) in the motor cortex enhanced neuronal growth and survival and improved locomotor function in the hindlimb. In addition, PDXK was confirmed as a target of miR-339 but not miR-124. MiR-339 knockout (KO) significantly increased the neurite outgrowth and decreased cell apoptosis in cortical neurons. Moreover, miR-339 KO rats exhibited functional recovery indicated by improved Basso, Beattie, and Bresnehan (BBB) score. Furthermore, bioinformatics prediction showed that PDXK was associated with GAP43, a crucial molecule related to neurite growth and functional improvement. The current research therefore confirmed that miR-339 targeting PDXK facilitated neurological recovery in the motor cortex of SCT rats, and the underlying mechanism was associated with regulating GAP43 in the remote cortex of rats subjected to SCT. These findings may uncover a new understanding of remoting cortex control following SCI and provide a new therapeutic strategy for the recovery of SCI in future clinical trials.

Administration of SB239063, a potent p38 MAPK inhibitor, alleviates acute lung injury induced by intestinal ischemia reperfusion in rats associated with AQP4 downregulation.

Acute lung injury (ALI), induced by intestinal ischemia reperfusion (II/R) injury, is characterized by pulmonary edema and inflammation. Aquaporin 4 (AQP4), has been pointed out recently involving in edema development. Previous studies have shown that p38 mitogen activated protein kinase (MAPK) activation resulted in lung inflammation, while p38 MAPK inhibitor can alleviate the pathology injury of lung tissue. However, the regulated mechanism of p38 MAPK in ALI induced by II/R is unclear. In this study, we established II/R rats' model by clamping the superior mesenteric artery (SMA) and coeliac artery (CA) for 40min and subsequent reperfusion for 16h, 24h, 48h. Subsequently, SB239063, a specific inhibitor of the activity of p38 MAPK, was injected (10mg/kg) intraperitoneally 60min before the operation. The severity of ALI was determined by histology analysis (HE staining and ALI scoring) and lung edema (lung wet/dry weight ratio) assessment. Western blot (WB) was applied to detect the expression level of AQP4 and phosphorylated (P)-p38 MAPK, and the localization of AQP4 was detected by immunofluorescent staining (IF). We found that AQP4 could express in the lung tissue. II/R could significantly induce lung injury, confirmed by lung injury scores and lung wet/dry weight ratios. The level of P-p38 MAPK and AQP4 were largely up-regulated in lung tissues. Moreover, inhibition of p38 MAPK activity could effectively down-regulate AQP4 expression and diminish the severity of II/R-induced ALI. These novel findings suggest that inhibition of p38 MAPK function should be a potential strategy for the prevention or treatment of ALI, by targeting AQP4 in future clinic trial.

Expression of lymphatic endothelium-specific hyaluronan receptor LYVE-1 in the developing mouse kidney.

Our knowledge of the embryonic development of the lymphatic vessels within the kidney is limited. The aim of this study was to establish the time of appearance and the distribution of intra-renal lymphatic vessels in the developing mouse kidney by using the lymphatic marker, LYVE-1. Kidneys from embryonic day 12 (E12) to E18, from neonates at post-natal day 1 (P1) to P21, and from adults were studied. In the adult mouse kidney, LYVE-1 was expressed mainly in the lymphatic endothelial cells (LECs) and in a subset of endothelial cells in the glomerular capillaries. However, in the developing mouse kidney, LYVE-1 was also expressed transiently in F4/80(+)/CD11b(-) immature macrophages/dendritic cells and in the developing renal vein. LYVE-1(+) lymphatic vessels connected with extra-renal lymphatics were detected in the kidney at E13. F4/80(+)/CD11b(-)/LYVE-1(+) immature macrophages/dendritic cells appeared prior to the appearance of LYVE-1(+) renal lymphatic vessels and were closely intermingled or even formed part of the lymphatic vascular wall. Prox1 was expressed only in the LYVE-1(+) LECs from fetus to adult-hood, but not in LYVE-1(+) endothelial cells of the developing renal vein and macrophages/dendritic cells. Thus, lymphatic vessels of the kidney might originate by extension of extra-renal lymphatics through an active branching process possibly associated with F4/80(+)/CD11b(-)/LYVE-1(+) macrophages/dendritic cells.