Research Center for Integrative Medicine, Affiliated Traditional Medicine Hospital of Southwest Medical University, Luzhou 646000, China.
Department of Medicine and Therapeutics and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong 999077, China.
Int J Mol Sci. 2021 Jul 23;22(15):7881. doi: 10.3390/ijms22157881.
Diabetic nephropathy (DN) is one of the most common complications in diabetes mellitus and the leading cause of end-stage renal disease. TGF-β is a pleiotropic cytokine and has been recognized as a key mediator of DN. However, anti-TGF-β treatment for DN remains controversial due to the diverse role of TGF-β1 in DN. Thus, understanding the regulatory role and mechanisms of TGF-β in the pathogenesis of DN is the initial step towards the development of anti-TGF-β treatment for DN. In this review, we first discuss the diverse roles and signaling mechanisms of TGF-β in DN by focusing on the latent versus active TGF-β1, the TGF-β receptors, and the downstream individual Smad signaling molecules including Smad2, Smad3, Smad4, and Smad7. Then, we dissect the regulatory mechanisms of TGF-β/Smad signaling in the development of DN by emphasizing Smad-dependent non-coding RNAs including microRNAs and long-non-coding RNAs. Finally, the potential therapeutic strategies for DN by targeting TGF-β signaling with various therapeutic approaches are discussed.
糖尿病肾病（DN）是糖尿病最常见的并发症之一，也是终末期肾病的主要原因。TGF-β 是一种多效细胞因子，已被认为是 DN 的关键介质。然而，由于 TGF-β1 在 DN 中的作用多样化，抗 TGF-β 治疗 DN 仍存在争议。因此，了解 TGF-β 在 DN 发病机制中的调节作用和机制是开发抗 TGF-β 治疗 DN 的第一步。在这篇综述中，我们首先通过关注潜伏型和活性 TGF-β1、TGF-β 受体以及下游单个 Smad 信号分子（包括 Smad2、Smad3、Smad4 和 Smad7），讨论了 TGF-β 在 DN 中的多种作用和信号机制。然后，我们通过强调包括 microRNAs 和长非编码 RNA 在内的 Smad 依赖性非编码 RNA，剖析了 TGF-β/Smad 信号在 DN 发展中的调节机制。最后，讨论了通过各种治疗方法靶向 TGF-β 信号转导治疗 DN 的潜在治疗策略。
