Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China.
Eur Rev Med Pharmacol Sci. 2018 May;22(10):3182-3189. doi: 10.26355/eurrev_201805_15079.
Evidence suggested that deficiency of autophagy is involved in the pathogenesis of diabetic nephropathy (DN). However, some recent studies have also shown that autophagy is activated in renal cells under diabetic conditions. In this review, we discuss whether autophagy is inactivated in renal cells in DN as well as the therapeutic potential of autophagy for treating DN, in order to aid future investigation in this field.
Relevant information, original research articles and reviews, were gathered primarily through a search in PubMed and Cochrane database. The activity and role of autophagy, as well as the relevant signaling pathways, were analyzed in different intrinsic renal cells, including podocyte, renal tubular epithelial cell, glomerular mesangial and endothelial cells.
The upstream of autophagic pathway, but not whole pathway, was predominately studied in these intrinsic renal cells, such as the induction of autophagy, an amount of autophagic vacuoles and so on. In most cases, autophagic inactivation occurred, which is an important mechanism underlying DN progression. Targeting the autophagic pathway to activate autophagy activity might have renoprotective effect. However, autophagic activation was also found in a few studies, in which there was a debate on the role of activated autophagy: mounting an adaptive response or leading to autophagic apoptosis.
The downstream of autophagic pathway, including the degradation of autophagic vacuoles, and lysosomal function, should be well studied to clarify the activity and role of autophagy in the progression of DN. Autophagy activation is likely a potential therapy for combatting DN.
有证据表明,自噬不足与糖尿病肾病(DN)的发病机制有关。然而,最近的一些研究也表明,在糖尿病条件下,自噬在肾脏细胞中被激活。在这篇综述中,我们讨论了自噬是否在 DN 中的肾脏细胞中失活,以及自噬治疗 DN 的治疗潜力,以帮助该领域的未来研究。
主要通过在 PubMed 和 Cochrane 数据库中搜索,收集了相关信息、原始研究文章和综述。分析了不同固有肾细胞(包括足细胞、肾小管上皮细胞、肾小球系膜和内皮细胞)中自噬的活性和作用,以及相关信号通路。
在这些固有肾细胞中,主要研究了自噬途径的上游,而不是整个途径,例如自噬的诱导、自噬小泡的数量等。在大多数情况下,发生了自噬失活,这是 DN 进展的重要机制。针对自噬途径激活自噬活性可能具有肾保护作用。然而,在一些研究中也发现了自噬的激活,对于激活的自噬的作用存在争议:是产生适应性反应还是导致自噬细胞凋亡。
应该深入研究自噬途径的下游,包括自噬小泡的降解和溶酶体功能,以阐明自噬在 DN 进展中的活性和作用。自噬激活可能是治疗 DN 的一种潜在疗法。