Sun Linlin, Ding Miao, Chen Fuhua, Zhu Dingyu, Xie Xinmiao
Nephrology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
PeerJ. 2023 Oct 16;11:e16170. doi: 10.7717/peerj.16170. eCollection 2023.
Diabetic nephropathy (DN) is a frequent microvascular complication of diabetes. Glomerular mesangial cell (MC) hypertrophy occurs at the initial phase of DN and plays a critical role in the pathogenesis of DN. Given the role of long non coding RNA (lncRNA) in regulating MC hypertrophy and extracellular matrix (ECM) accumulation, our aim was to identify functional lncRNAs during MC hypertrophy.
Here, an lncRNA, C920021L13Rik (L13Rik for short), was identified to be up-regulated in DN progression. The expression of L13Rik in DN patients and diabetic mice was assessed using quantitative real-time PCR (qRT-PCR), and the function of L13Rik in regulating HG-induced MC hypertrophy and ECM accumulation was assessed through flow cytometry and western blotting analysis.
The L13Rik levels were significantly increased while the miR-2861 levels were decreased in the peripheral blood of DN patients, the renal tissues of diabetic mice, and HG-treated MCs. Functionally, both L13Rik depletion and miR-2861 overexpression effectively reduced HG-induced cell hypertrophy and ECM accumulation. Mechanistically, L13Rik functioned as a competing endogenous RNA (ceRNA) to sponge miR-2861, resulting in the de-repression of cyclin-dependent kinase inhibitor 1B (CDKN1B), a gene known to regulate cell cycle and MC hypertrophy.
Collectively, the current results demonstrate that up-regulated L13Rik is correlated with DN and may be a hopeful therapeutic target for DN.
糖尿病肾病（DN）是糖尿病常见的微血管并发症。肾小球系膜细胞（MC）肥大发生在DN的初始阶段，在DN的发病机制中起关键作用。鉴于长链非编码RNA（lncRNA）在调节MC肥大和细胞外基质（ECM）积累中的作用，我们的目的是鉴定MC肥大过程中的功能性lncRNA。
在此，我们鉴定出一种lncRNA，C920021L13Rik（简称L13Rik）在DN进展过程中上调。使用定量实时PCR（qRT-PCR）评估L13Rik在DN患者和糖尿病小鼠中的表达，并通过流式细胞术和蛋白质免疫印迹分析评估L13Rik在调节高糖（HG）诱导的MC肥大和ECM积累中的作用。
在DN患者的外周血、糖尿病小鼠的肾组织以及HG处理的MC中，L13Rik水平显著升高，而miR-2861水平降低。在功能上，L13Rik缺失和miR-2861过表达均有效减少了HG诱导的细胞肥大和ECM积累。机制上，L13Rik作为竞争性内源RNA（ceRNA）发挥作用，吸附miR-2861，导致细胞周期蛋白依赖性激酶抑制剂1B（CDKN1B）去抑制，CDKN1B是一种已知调节细胞周期和MC肥大的基因。
总体而言，目前的结果表明L13Rik上调与DN相关，可能是DN有希望的治疗靶点。
