Lian Zhiwen, Ke Guibao, Zhang Hong, Dou Caoshuai, Chen Xueqin, Li Bohou, Zhang Fengxia, Wen Shichun, Wu Qiong, Xia Yubin, Jiang Nan, Li Zhuo, Li Sijia, Zhao Xingchen, Ma Jianchao, Lin Ting, Wen Feng, Xu Lixia, Li Zhilian, Liang Huabang, Dong Wei, Chen Yuanhan, Li Ruizhao, Ye Zhiming, Wang Wenjian, Liang Xinling, Shi Wei, Zhang Li, Liu Shuangxin
Department of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
Department of Nephrology, Foshan First People's Hospital, Foshan, China.
Biochem Biophys Rep. 2021 Oct 21;28:101145. doi: 10.1016/j.bbrep.2021.101145. eCollection 2021 Dec.
Podocyte injury is sufficient to cause glomerulosclerosis and proteinuria, eventually leading to kidney failure. Previous studies found that podocytes and neurons had similar biological characteristics. Growth-associated protein-43 (GAP-43) is a growth cone protein in neurons, and a marker of axonal and synaptic growth. However, it is not known whether GAP-43 is expressed in podocytes. Compared with normal glomerular podocytes, GAP-43 was significantly reduced in patients with glomerular diseases. GAP-43 also significantly reduced in lipopolysaccharide (LPS)-treated podocytes. We found that the decreased expression of nephrin, the cell marker of the podocyte, was significantly recovered with GAP-43 overexpression. In contrast, the migration ability in LPS-treated podocyte was reduction after GAP-43 overexpressing. Moreover, overexpression of GAP-43 attenuated podocyte apoptosis by up-regulating the ratio of Bcl-2/Bax with LPS treatment. Finally, Plaue and Rcan1 which are downstream target gene of NFATc1 decreased with overexpression of GAP-43 podocytes. We concluded that GAP-43 attenuated podocyte injury by inhibiting calcineurin/NFATc1 signaling. The findings may provide a promising treatment for podocyte injury-related diseases.
足细胞损伤足以导致肾小球硬化和蛋白尿，最终导致肾衰竭。先前的研究发现足细胞和神经元具有相似的生物学特性。生长相关蛋白43（GAP - 43）是神经元中的一种生长锥蛋白，是轴突和突触生长的标志物。然而，尚不清楚GAP - 43是否在足细胞中表达。与正常肾小球足细胞相比，肾小球疾病患者的GAP - 43显著降低。在脂多糖（LPS）处理的足细胞中，GAP - 43也显著降低。我们发现，足细胞的细胞标志物nephrin的表达降低在GAP - 43过表达后显著恢复。相反，在GAP - 43过表达后，LPS处理的足细胞的迁移能力降低。此外，GAP - 43的过表达通过在LPS处理时上调Bcl - 2/Bax的比例来减轻足细胞凋亡。最后，作为NFATc1下游靶基因的Plaue和Rcan1在GAP - 43过表达的足细胞中降低。我们得出结论，GAP - 43通过抑制钙调神经磷酸酶/NFATc1信号传导来减轻足细胞损伤。这些发现可能为足细胞损伤相关疾病提供一种有前景的治疗方法。
