Open Access Open Access  Restricted Access Subscription Access
Cover Image

Nod2 silencing is involved in the protective role of Calycosin in diabetic nephropathy cell model

Di Huang, Peicheng Shen, Chen Wang, Jiandong Gao, Chaoyang Ye, Feng Wu

Abstract


Diabetic nephropathy (DN) is considered as the most serious diabetic microvascular complication. Podocyte injury has a crucial role in the pathogenesis of DN. Calycosin, a major active component of a Traditional Chinese Medicine (TCM), has been found to play a protective role in DN. However, the mechanism has not been well discovered. In this study, high D-Glucose (D-Glu) was used to treat podocytes to establish podocyte DN cell model. DCFH-DA probe and annexin V/PI staining kit were used to detect Reactive Oxygen Species (ROS) level and cell apoptosis, respectively. Firstly, Nod2 expression level was upregulated after treatment with D-Glu. Then, D-Glu induced cell apoptosis and production of ROS, but Calycosin and Nod2 silencing alleviated these effects. Further, the decrease of nephrin and podocalyxin induced by D-Glu could be blocked by Calycosin and Nod2 silencing. Increase protein level of p-p38 induced by D-Glu was ameliorated by Calycosin and Nod2 silencing. In addition, Nod2 overexpression enhanced the apoptosis rates, the production of ROS, and the protein level of p-p38, but these effects were ameliorated by Calycosin. In conclusion, knockdown of Nod2 participated in the protection of Calycosin in D-Glu induced DN cell model via p38-MAPK signaling.


Keywords


Calycosin, Nod2, DN, p38.

Full Text:

PDF

References


Allison, S.J., 2012. Podocyte biology: a new regulator of podocytes. Nat. Rev. Nephrol., 8, 683.

Dai, H., et al., 2017. Research progress on mechanism of podocyte depletion in diabetic nephropathy. J. Diabetes Res., 2615286.

Doublier, S., et al., 2001. Nephrin redistribution on podocytes is a potential mechanism for proteinuria in patients with primary acquired nephrotic syndrome. Am. J. Pathol., 158, 1723-1731.

Drossopoulou, G.I., et al., 2009. Impaired transcription factor interplay in addition to advanced glycation end products suppress podocalyxin expression in high glucose-treated human podocytes. Am. J. Physiol. Renal Physiol., 297, F594-603.

Drummond, K., et al., 2002. The early natural history of nephropathy in type 1 diabetes: II. Early renal structural changes in type 1 diabetes. Diabetes, 51, 1580-1587.

Du, P., et al., 2013. NOD2 promotes renal injury by exacerbating inflammation and podocyte insulin resistance in diabetic nephropathy. Kidney Int., 84, 265-276.

Elsherbiny, N.M., et al., 2020. Renoprotective effect of calycosin in high fat diet-fed/STZ injected rats: Effect on IL-33/ST2 signaling, oxidative stress and fibrosis suppression. Chemico-Biol. Interact., 315, 108897.

Gao, Y., et al., 2012. Radix Astragali lowers kidney oxidative stress in diabetic rats treated with insulin. Endocrine, 42, 592-598.

Garibotto, G., et al., 2017. Toll-like receptor-4 signaling mediates inflammation and tissue injury in diabetic nephropathy. J. Nephrol., 30, 719-727.

Gnudi, L., et al., 2016. Diabetic nephropathy: perspective on novel molecular mechanisms. Trends Endocrinol. Metabol., TEM, 27, 820-830.

Lin, M., et al., 2012. Toll-like receptor 4 promotes tubular inflammation in diabetic nephropathy. J. Am. Soc. Nephrol., JASN, 23, 86-102.

Maezawa, Y., et al., 2015. Cell biology of diabetic nephropathy: Roles of endothelial cells, tubulointerstitial cells and podocytes. J. Diabetes Investig., 6, 3-15.

Magalhaes, J.G., et al., 2011. What is new with Nods? Curr. Opin. Immunol., 23, 29-34.

Navarro-Gonzalez, J.F., et al., 2011. Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathy. Nat. Rev. Nephrol., 7, 327-340.

Ren, M., et al., 2016. Calycosin-7-Obeta-D-glucoside attenuates ischemiareperfusion injury in vivo via activation of the PI3K/Akt pathway. Mol. Med. Rep., 13, 633-640.

Shang, J., et al., 2015. Identification of NOD2 as a novel target of RNA-binding protein HuR: evidence from NADPH oxidase-mediated HuR signaling in diabetic nephropathy. Free Radic. Biol. Med., 79, 217-227.

Shang, J., et al., 2017. NOD2 promotes endothelial-to-mesenchymal transition of glomerular endothelial cells via MEK/ERK signaling pathway in diabetic nephropathy. Biochem. Biophys. Res. Comm., 484, 435-441.

Shaw, M.H., et al., 2011. The ever-expanding function of NOD2: autophagy, viral recognition, and T cell activation. Trends Immunol., 32, 73-79.

Susztak, K., et al., 2006. Glucose-induced reactive oxygen species cause apoptosis of podocytes and podocyte depletion at the onset of diabetic nephropathy. Diabetes, 55, 225-233.

Takeda, T., et al., 2001. Loss of glomerular foot processes is associated with uncoupling of podocalyxin from the actin cytoskeleton. J. Clin. Investig., 108, 289-301.

Tang, D., et al., 2011. Inhibitory effects of two major isoflavonoids in Radix Astragali on high glucose-induced mesangial cells proliferation and AGEs-induced endothelial cells apoptosis. Plant. Med., 77, 729-732.

Ting, J.P., et al., 2010. How the noninflammasome NLRs function in the innate immune system. Sci., 327, 286-290.

Trohatou, O., et al., 2017. Vitamin D3 ameliorates podocyte injury through the nephrin signalling pathway. J. Cell. Mol. Med., 21, 2599-2609.

Umanath, K., et al., 2018. Update on diabetic nephropathy: core curriculum 2018. Am. J. Kidney Dis., Offic. J. Natl. Kidney Found., 71, 884-895.

Wada, J., et al., 2016. Innate immunity in diabetes and diabetic nephropathy. Nat. Rev. Nephrol., 12, 13-26.

Welsh, G.I., et al., 2010. Nephrin-signature molecule of the glomerular podocyte? J. Pathol., 220, 328-337.

Xu, Y., et al., 2015. Calycosin rebalances advanced glycation end products-induced glucose uptake dysfunction of hepatocyte in vitro. Am. J. Chin. Med., 43, 1191-1210.

Zhang, Y.Y., et al., 2019. Calycosin Ameliorates diabetes-induced renal inflammation via the NF-kappaB pathway in vitro and in vivo. Med. Sci. Mon., Int. Med. J. Exp. Clin. Res., 25, 1671-1678.

Zhao, L., et al., 2011. NOD1 activation induces proinflammatory gene expression and insulin resistance in 3T3-L1 adipocytes. Am. J. Physiol. Endocrinol. Metabol., 301, E587-E598.


Refbacks

  • There are currently no refbacks.