CK2通过GLO1磷酸化调节NF-κB促进糖尿病肾脏纤维化的作用研究

糖尿病肾脏纤维化病变是肾脏慢性炎性反应的观点受到高度重视。申请人前期已证实蛋白激酶CK2对糖尿病肾脏炎性纤维化成分起关键调节作用，然而其影响炎性活化的机制尚需进一步阐明。申请人近期研究发现GLO1可能参与糖尿病肾脏炎性纤维化的病理进程；GLO1可能通过调控NF-κB炎症核因子影响糖尿病肾病；GLO1与CK2可能存在相互作用并受CK2调节。据此申请人提出假说：CK2通过促进GLO1磷酸化、调节其活化，影响MGO水平，参与NF-κB炎症核因子介导的糖尿病肾脏纤维化。基于此，本项目拟采用基因工程大鼠、小分子RNAi、蛋白质相互作用等体内外实验手段开展以下研究：确证GLO1在调控糖尿病肾脏炎性纤维化病变的作用；阐明GLO1介导CK2调控糖尿病肾病的分子机制；探讨GLO1与CK2蛋白质相互作用。通过本课题的实施，将可能揭示CK2调节糖尿病肾病的新机制，为寻找抗糖尿病肾病的新策略提供更充分的科学依据。

The view that diabetic renal fibrosis is a chronic inflammatory response of the kidney has been highly valued. The applicant has previously demonstrated that protein kinase CK2 plays a key regulatory role in the components of diabetic renal inflammatory fibrosis, but the mechanism of its influence on inflammatory activation still needs to be further clarified. Recent studies have found that GLO1 may be involved in the pathological process of diabetic renal inflammatory fibrosis. GLO1 may affect diabetic nephropathy by regulating inflammatory nuclear factor NF-κB. GLO1 and CK2 may interact with each other and be regulated by CK2. Based on this, the applicant hypothesizes that CK2 is involved in diabetic renal fibrosis mediated by NF-κB via promoting GLO1 phosphorylation and regulating its activation, affecting MGO levels. Based on this, this project intends to follow in vivo and in vitro experimental methods such as genetically engineered rats, small interference RNA and protein interaction to carry out the following research: To confirm the role of GLO1 in regulating diabetic renal inflammatory fibrosis; To elucidate the molecular mechanism of CK2 regulation on diabetic nephropathy via GLO1; To investigate the protein interaction between GLO1 and CK2. Through the implementation of this project, it is possible to reveal the new mechanism of CK2 regulating diabetic nephropathy, so as to provide a more adequate scientific basis for finding new strategies against diabetic nephropathy.