Astragalus membranaceus up-regulate Cosmc expression and reverse IgA dys-glycosylation in IgA nephropathy

BMC Complementary and Alternative Medicine

Wei Qin³  Wanxing Tang³  Junming Fan¹  Lichuan Yang³  Zi Li³  Xiang Zhong²  XiaoLei Chen³  Ling Ji³ 

[1] State Key Laboratory of Biotherapy of Sichuan University, Chengdu, Sichuan, China;Division of Nephrology, Sichuan Provincial People’s Hospital, Chengdu, Sichuan, China;Division of Nephrology, Department of Medicine, West China Hospital of Sichuan University, 37 # Guoxue road, Wuhou District, Chengdu, Sichuan, China

关键词: Glycosylation;    Cosmc;    Astragalus membranaceus;    IgA nephropathy;   

Others  :  830067
DOI  :  10.1186/1472-6882-14-195

 received in 2013-05-27, accepted in 2014-06-12,  发布年份 2014

【 摘 要 】

Background

Decreased Core I β3-Gal-T-specific molecular chaperone (Cosmc) expression induced IgA1 aberrant glycosylation is the main characteristic of IgA nephropathy (IgAN). This study tried to elucidate the effect of Astragalus membranaceus on Cosmc expression and IgA O-glycosylation of peripheral B lymphocytes in IgAN patients.

Methods

Peripheral B lymphocytes of 21 IgAN patients and 10 normal controls were isolated and cultured with or without lipopolysaccharide (LPS) and Astragalus membranaceus injection (AMI). Cosmc mRNA and protein expression levels were measured by real-time RT-PCR and Western blot. IgA1 and glycosylation level were determined by enzyme-linked immunosorbent assay (ELISA) and VV lectin-binding method.

Results

Cosmc mRNA expression and IgA1 O-glycosylation level in IgAN patients was significantly lower than normal controls at baseline. Treatment of LPS could obviously inhibit Cosmc expression and increase the IgA1 secretion in peripheral B lymphocytes of IgAN patients, which resulted in a significantly increase in IgA1 aberrant glycosylation level. Addition of AMI could remarkably up regulated Cosmc expression, decrease IgA1 secretion, and reverse glycosylation level in a dose related manner.

Conclusion

AMI can up-regulate Cosmc expression of peripheral B lymphocytes and reverse IgA1 aberrant O-glycosylation level, which might be the underlying mechanism of AMI therapy in treating IgAN.

Trial registration

TCTR20140515001 (Registration Date: 2014-05-15)

【 授权许可】

   
2014 Ji et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】

• [1]Lai KN: Pathogenesis of IgA nephropathy. Nat Rev Nephrol 2012, 8:275-283.
• [2]Suzuki H, Kiryluk K, Novak J, Moldoveanu Z, Herr AB, Renfrow MB, Wyatt RJ, Scolari F, Mestecky J, Gharavi AG, Julian BA: The pathophysiology of IgA nephropathy. J Am Soc Nephrol 2011, 22:1795-1803.
• [3]Qin W, Zhou Q, Yang LC, Li Z, Su BH, Luo H, Fan JM: Peripheral B lymphocyte beta1,3-galactosyltransferase and chaperone expression in immunoglobulin A nephropathy. J Intern Med 2005, 258:467-477.
• [4]Li M, Wang W, Xue J, Gu Y, Lin S: Meta-analysis of the clinical value of Astragalus membranaceus in diabetic nephropathy. J Ethnopharmacol 2011, 133:412-419.
• [5]Li SM, Yan JX, Yang L: Effects of Astragalus injection on renal tubular function in patients with IgA nephropathy. Zhongguo Zhong Xi Yi Jie He Za Zhi 2006, 26:504-507.
• [6]Qin W, Zhong X, Fan JM, Zhang YJ, Liu XR, Ma XY: External suppression causes the low expression of the Cosmc gene in IgA nephropathy. Nephrol Dial Transplant 2008, 23:1608-1614.
• [7]Xie LS, Qin W, Fan JM, Huang J, Xie XS, Li Z: The role of C1GALT1C1 in lipopolysaccharide-induced IgA1 aberrant O-glycosylation in IgA nephropathy. Clin Invest Med 2010, 33:E5-E13.
• [8]Xie L, Tan C, Fan J, Fu P, Tang Y, Tao Y, Qin W: Mycophenolic acid reverses IgA1 aberrant glycosylation through up-regulating Cosmc expression in IgA nephropathy. Int Urol Nephrol 2013, 45:571-579.
• [9]Giannakakis K, Feriozzi S, Perez M, Faraggiana T, Muda AO: Aberrantly glycosylated IgA1 in glomerular immune deposits of IgA nephropathy. J Am Soc Nephrol 2007, 18:3139-3146.
• [10]Zhao N, Hou P, Lv J, Moldoveanu Z, Li Y, Kiryluk K, Gharavi AG, Novak J, Zhang H: The level of galactose-deficient IgA1 in the sera of patients with IgA nephropathy is associated with disease progression. Kidney Int 2012, 82:790-796.
• [11]Meng L, Qu L, Tang J, Cai SQ, Wang H, Li X: A combination of Chinese herbs, Astragalus membranaceus var. mongholicus and Angelica sinensis, enhanced nitric oxide production in obstructed rat kidney. Vascul Pharmacol 2007, 47:174-183.
• [12]Zuo C, Xie XS, Qiu HY, Deng Y, Zhu D, Fan JM: Astragalus mongholicus ameliorates renal fibrosis by modulating HGF and TGF-beta in rats with unilateral ureteral obstruction. J Zhejiang Univ Sci B 2009, 10:380-390.
• [13]Peng XJ, Wu XC, Zhang GZ, Yi ZW, Zheng WM, He XJ, Mo SH, Tan H: Regulatory effect of Astragalus membranaceus on the immune disorder in rats with IgA nephropathy. Zhonghua Er Ke Za Zhi 2008, 46:55-60.
• [14]Cho WC, Leung KN: In vitro and in vivo immunomodulating and immunorestorative effects of Astragalus membranaceus. J Ethnopharmacol 2007, 113:132-141.
• [15]Floege J, Eitner F: Current therapy for IgA nephropathy. J Am Soc Nephrol 2011, 22:1785-1794.