Center for Organ Fibrosis and Remodeling Research, Jiangsu Key Lab of Molecular Medicine, Nanjing University School of Medicine, Nanjing, China.
J Mol Med (Berl). 2021 May;99(5):581-592. doi: 10.1007/s00109-021-02044-8. Epub 2021 Feb 6.
Developments of many renal diseases are substantially influenced by epigenetic modifications of numerous genes, mainly mediated by DNA methylations, histone modifications, and microRNA interference; however, not all gene modifications causally affect the disease onset or progression. Klotho is a critical gene whose repressions in various pathological conditions reportedly involve epigenetic regulatory mechanisms. Klotho is almost unexceptionally repressed early after acute or chronic renal injuries and its levels inversely correlated with the disease progression and severity. Moreover, the strategies of Klotho derepression via epigenetic modulations beneficially change the pathological courses both in vitro and in vivo. Hence, Klotho is not only considered a biomarker of the renal disease but also a potential or even an ideal target of therapeutic epigenetic intervention. Here, we summarize and discuss studies that investigate the Klotho repression and intervention in renal diseases from an epigenetic point of view. These information might shed new sights into the effective therapeutic strategies to prevent and treat various renal disorders.
许多肾脏疾病的发展在很大程度上受到许多基因的表观遗传修饰的影响,主要通过 DNA 甲基化、组蛋白修饰和 microRNA 干扰来介导;然而,并非所有基因修饰都能因果性地影响疾病的发生或进展。Klotho 是一个关键基因,其在各种病理条件下的抑制作用据报道涉及表观遗传调控机制。Klotho 在急性或慢性肾损伤后早期几乎无一例外地受到抑制,其水平与疾病的进展和严重程度呈负相关。此外,通过表观遗传调控使 Klotho 去抑制的策略在体外和体内都有益地改变了病理过程。因此,Klotho 不仅被认为是肾脏疾病的生物标志物,而且是治疗性表观遗传干预的潜在甚至理想靶点。在这里,我们从表观遗传学的角度总结和讨论了研究 Klotho 抑制和干预肾脏疾病的研究。这些信息可能为预防和治疗各种肾脏疾病提供有效的治疗策略提供新的思路。