SENP7去类泛素化修饰AQP4诱导高尔基体应激介导Apelin-13促心肌细胞肥大

申请者最新报道压应力感受器APJ受体的内源性配体Apelin-13激活铁自噬促心肌细胞肥大，文献报道铁自噬与高尔基体应激密切相关，AQP4参与氧化应激，且预测AQP4具有类泛素化修饰位点。预实验发现Apelin-13抑制去类泛素化酶SENP7，促进AQP4表达，诱导高尔基体应激。据此提出“SENP7去类泛素化修饰AQP4诱导高尔基体应激介导Apelin-13促心肌细胞肥大”的科学假说。课题采用基因敲除等技术明确Apelin-13抑制SENP7去类泛素化修饰AQP4；阐明SENP7去类泛素化修饰AQP4调控Apelin-13诱导的高尔基体应激；揭示SENP7去类泛素化修饰AQP4诱导高尔基体应激介导Apelin-13促心肌细胞肥大。课题从SENP7去类泛素化修饰AQP4、高尔基体应激等视角揭示Apelin-13/APJ促心肌细胞肥大的分子机理，为APJ受体成为心肌肥厚治疗新靶点提供实验依据。

Applicant recently reported that the endogenous ligand of stressor receptor APJ receptor, Apelin-13 activate ferritinophagy to promote cardiomyocyte hypertrophy. The literature reports that ferritinophagy is closely related to Golgi apparatus stress and AQP4 is involved in oxidative stress. AQP4 is predicted to have a ubiquitin-like modification site. Preliminary experiments found that Apelin-13 inhibits the deubiquitination-like enzyme SENP7, promotes AQP4 expression, and induces Golgi apparatus stress. Based on this, the scientific hypothesis that "The desumoylation of AQP4 mediated by SENP7-Golgi apparatus stress pathway promotes cardiomyocytes hypertrophy induced by apelin-13" is proposed. Applicant will adopt gene-knockout and other techniques to clarify that Apelin-13 inhibits the desumoylation of AQP4 induced by SENP7; illustrate whether the desumoylation of AQP4 induced by SENP7 can mediate the Golgi apparatus stress triggered by apelin-13; reveal whether the desumoylation of AQP4 induced by SENP7-Golgi apparatus stress pathway can mediate cardiomyocyte hypertrophy induced by Apelin-13. This project is able to uncover the molecular mechanism of the cardiomyocytes hypertrophy promoted by apelin-13 from the unique perspective of the Golgi apparatus stress and the desumoylation of AQP4 induced by SENP7, and provides experimental basis for APJ receptor to become a new target for cardiac hypertrophy treatment.