Yu Rucui, Wu Ruiying, Chen Tingting, Xu Jingwei
Department of Traditional Chinese Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China.
Department of Traditional Chinese Medicine, The First Clinical Medical School of Anhui University of Traditional Chinese Medicine, Hefei, Anhui, 230001, China.
J Food Drug Anal. 2025 Jun 13;33(2):172-178. doi: 10.38212/2224-6614.3545.
Diabetic nephropathy (DN) is one dominating reason for death in diabetic patients, and its incidence is high. It has been reported that Yiqi Yangyin Tongluo prescription (YYTP) can relieve inflammation, and it owns better clinical effects in the treatment of DN. However, the molecular mechanisms of YYTP in the treatment of DN still keep unclear, and deeply investigations are needed. In this study, it firstly was manifested that YYTP can repress the lncRNA VIM-antisense 1 (VIM-AS1) expression in high glucose (HG)-evoked HK-2 cells. Overexpression of VIM-AS1 roll-backed the inhibitive impacts of YYTP on cell apoptosis in HG-triggered HK-2 cells. Additionally, it was uncovered that the attenuated autophagy of LC3B in HG-triggered HK-2 cells was counteracted after 20% YYTP treatment, but this phenomenon was further attenuated after VIM-AS1 amplification. Besides, VIM-AS1 can pull down FOXK2 protein, and overexpression of VIM-AS1 counteracted the suppressive effects of YYTP on forkhead box K2 (FOXK2)/mammalian target of rapamycin (mTOR) in HG-mediated HK-2 cells. In conclusion, it was firstly disclosed that YYTP targeted lncRNA VIM-AS1 to regulate FOXK2/mTOR to promote autophagy and inhibit cell apoptosis in DN progression. This discovery hinted that YYTP may be one valid drug for DN therapy.
糖尿病肾病（DN）是糖尿病患者死亡的主要原因之一，其发病率很高。据报道，益气养阴通络方（YYTP）可以减轻炎症，在DN治疗中具有较好的临床效果。然而，YYTP治疗DN的分子机制仍不清楚，需要深入研究。在本研究中，首先表明YYTP可以抑制高糖（HG）诱导的HK-2细胞中lncRNA VIM反义1（VIM-AS1）的表达。VIM-AS1的过表达逆转了YYTP对HG触发的HK-2细胞凋亡的抑制作用。此外，还发现20%YYTP处理后，HG触发的HK-2细胞中LC3B自噬减弱的现象被抵消，但VIM-AS1扩增后这种现象进一步减弱。此外，VIM-AS1可以下拉FOXK2蛋白，VIM-AS1的过表达抵消了YYTP对HG介导的HK-2细胞中叉头盒K2（FOXK2）/雷帕霉素哺乳动物靶蛋白（mTOR）的抑制作用。总之，首次揭示YYTP靶向lncRNA VIM-AS1调节FOXK2/mTOR以促进自噬并抑制DN进展中的细胞凋亡。这一发现提示YYTP可能是治疗DN的有效药物。
