Pathophysiology of Diabetic Complications Laboratory, Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
Pathophysiology of Diabetic Complications Laboratory, Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia
Clin Sci (Lond). 2019 Jan 25;133(2):287-313. doi: 10.1042/CS20180438. Print 2019 Jan 31.
The incidence of chronic kidney diseases (CKDs) is expected to rise, fuelled by the ever increasing epidemic of Type 2 diabetes. Despite extensive research in this area, there are currently no effective treatments available to sufficiently halt the progression of CKD towards renal failure. This is largely due to ongoing secondary pathological processes generally elicited by the onset of disease. Fibrosis, in particular, is a prominent pathological hallmark of many forms of CKD and considered to be a central contributing factor for the progression of CKD towards end-stage renal disease. Transforming growth factor β (TGFβ) has been implicated to be a major regulatory cytokine in CKD, especially in fibrosis development, and reduced TGFβ signalling activity has been previously shown to be associated with improved renal outcomes in experimental animal studies. A number of molecules related to and/or interacting with the TGFβ signalling pathway have been identified as potential therapeutic targets. However, due to its pleiotropic nature, complete inhibition of the TGFβ signalling pathway is likely to lead to deleterious side effects. Therefore, a better understanding of this pathway and the molecules modulating this pathway is necessary to develop more efficacious and therapeutic strategies to combat progression of CKD.
慢性肾脏病 (CKD) 的发病率预计会上升,这主要是由于 2 型糖尿病的流行日益加剧。尽管在这一领域进行了广泛的研究,但目前尚无有效的治疗方法可以充分阻止 CKD 向肾衰竭发展。这在很大程度上是由于疾病发作时通常会引发持续的继发性病理过程。纤维化是许多形式的 CKD 的一个突出的病理标志,被认为是 CKD 向终末期肾病进展的一个核心因素。转化生长因子 β (TGFβ) 已被认为是 CKD 的主要调节细胞因子,特别是在纤维化发展中,以前的研究表明,TGFβ 信号活性降低与实验动物研究中的改善肾脏预后相关。已经确定了许多与 TGFβ 信号通路相关和/或相互作用的分子作为潜在的治疗靶点。然而,由于其多效性,完全抑制 TGFβ 信号通路可能会导致有害的副作用。因此,需要更好地了解该途径以及调节该途径的分子,以开发更有效和更具治疗性的策略来对抗 CKD 的进展。
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