Wu Keqian, Peng Rui, Mu Qiuyu, Jiang Yongxue, Chen Jingshou, Ming Rui, Zhao Jie, Zhang Zheng, Sun Yan
Department of Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.
Department of Bioinformatics, Chongqing Medical University, Chongqing, China.
Open Med (Wars). 2022 May 26;17(1):978-990. doi: 10.1515/med-2022-0487. eCollection 2022.
Diabetic nephropathy (DN) is one of the chronic microvascular diseases of diabetes. Studies revealed that inflammation is involved in the development of DN. However, its mechanisms are not fully clear. Here, we screened DN-related mRNAs by RNA sequencing in the renal tissues of db/db DN mice and normal control mice. The Swiss-Model, ZDOCK 3.0.2 and PyMOL 2.3.2 were applied for bioinformatics analysis. In total, we obtained 6,820 mRNAs that were dysexpressed in DN. Among them, Receptor for Activated C Kinase 1 (Rack1) was focused on for its high fold changes and high values of fragments per kilobase million (FPKM) in both two groups (FPKM >100). Moreover, Rack1 was highly expressed in DN and . Results displayed that the expressions of pro-inflammatory cytokines Mcp-1 and Tnf-α were increased when Rack1 was overexpressed in cells cultured with low glucose while the expressions of Mcp-1 and Tnf-α were decreased when Rack1 was silenced in cells cultured with high glucose. Furthermore, results showed that the established DN inflammatory factor nuclear factor NF-kappa-B (NF-κB) was regulated by Rack1 via the direct interaction between Rack1 and NF-κB subunits P50 and P65. In summary, this identified Rack1 could play an important role in the inflammation of DN via NF-κB, which can provide new insight for DN research.
糖尿病肾病（DN）是糖尿病的慢性微血管疾病之一。研究表明，炎症参与了DN的发展。然而，其机制尚不完全清楚。在此，我们通过RNA测序在db/db DN小鼠和正常对照小鼠的肾组织中筛选了与DN相关的mRNA。应用Swiss-Model、ZDOCK 3.0.2和PyMOL 2.3.2进行生物信息学分析。总共，我们获得了6820个在DN中表达异常的mRNA。其中，活化C激酶1受体（Rack1）因其在两组中的高倍数变化和高每千碱基百万片段值（FPKM）（FPKM>100）而受到关注。此外，Rack1在DN中高表达。结果显示，在低糖培养的细胞中过表达Rack1时，促炎细胞因子Mcp-1和Tnf-α的表达增加，而在高糖培养的细胞中沉默Rack1时，Mcp-1和Tnf-α的表达降低。此外，结果表明，已确定的DN炎症因子核因子NF-κB（NF-κB）通过Rack1与NF-κB亚基P50和P65之间的直接相互作用受Rack1调节。总之，本研究确定Rack1可通过NF-κB在DN炎症中发挥重要作用，这可为DN研究提供新的见解。
