Bayer AG.

Yes-associated protein (YAP) transcriptional coactivator is negatively regulated by the Hippo pathway and functions in controlling the size of multiple organs, such as liver during development. However, it is not clear whether YAP signaling participates in the process of the formation of glia scars after spinal cord injury (SCI). In this study, we found that YAP was upregulated and activated in astrocytes of C57BL/6 male mice after SCI in a Hippo pathway-dependent manner. Conditional knockout (KO) of yap in astrocytes significantly inhibited astrocytic proliferation, impaired the formation of glial scars, inhibited the axonal regeneration, and impaired the behavioral recovery of C57BL/6 male mice after SCI. Mechanistically, the bFGF was upregulated after SCI and induced the activation of YAP through RhoA pathways, thereby promoting the formation of glial scars. Additionally, YAP promoted bFGF-induced proliferation by negatively controlling nuclear distribution of p27 Kip1 mediated by CRM1. Finally, bFGF or XMU-MP-1 (an inhibitor of Hippo kinase MST1/2 to activate YAP) injection indeed activated YAP signaling and promoted the formation of glial scars and the functional recovery of mice after SCI. These findings suggest that YAP promotes the formation of glial scars and neural regeneration of mice after SCI, and that the bFGF-RhoA-YAP-p27 Kip1 pathway positively regulates astrocytic proliferation after SCI.

The incidence of malignant tumours is rising worldwide. Cancer is regarded as the leading cause of death and the most key obstacle to improve life expectancy in every country of the world in the 21st century. 1 Tumour is a new organism formed by the proliferation of local tissue cells under the action of various tumorigenic factors. The development of cancer consists of a number of complex stages of initiation, progression and promotion, in which the stage of progression is invertible which seems to be the phase for the most appropriate drug intervention. Although there are different types therapies targeting cancers, such as surgical resection, radiotherapy, chemotherapy, immunotherapy, biotherapy therapy, molecular-targeted therapy and treatment of TCM, however, not every therapy achieves the expected optimal effect results. For instance, surgical resection can remove the tumour, the risk of advanced cancer is increased, and the survival rate is reduced. Clinical combination of first-line chemotherapy drugs and radiotherapy can prevent the progress of cancer to some extent, but they may cause serious toxic effects, affect the metabolism and proliferation of normal tissues, and reduce the life quality of patients.

No abstract

No abstract