Role of Human Mesangial-Tubular Crosstalk in Secretory IgA-Induced IgA Nephropathy

Author:

Zhang Junjun,Zhou Ruwen,Mi Yiming,Liu Zhangsuo,Huang Bo,Guo Ruxue,Wang Panfei,Quan Songxia,Zhou Yali

Abstract

<b><i>Background:</i></b> IgA nephropathy (IgAN) is characterized by the mesangial deposition of pathogenic IgA. We previously detected the deposition of pathogenic secretory IgA (SIgA) in the mesangium of about one-third of IgAN patients. Tubulointerstitial injury has an important role in the development of IgAN. However, the relationship between SIgA and tubulointerstitial damage is currently unclear. In this work, the role of the mesangial-tubular crosstalk was explored in the tubulointerstitial damage in SIgA-induced IgAN. <b><i>Methods:</i></b> SIgA deposition in renal tissues of IgAN patients was detected by immunofluorescence. Flow cytometry was used to assess the binding of SIgA to human renal mesangial cells (HRMC) and human proximal tubule epithelial (HK-2) cells. HK-2 was co-cultured with HRMC added with SIgA isolated from patients or normal volunteers. Protein synthesis and gene expressions of TNF-α, TGF-β1, and MCP-1 were determined by ELISA and PCR, respectively. The expressions of the above cytokines in renal tissues of patients and normal controls were detected by immunohistochemistry. <b><i>Results:</i></b> Twenty-nine of 96 patients had SIgA deposition in the mesangium, but SIgA was rarely detected in the tubulointerstitium. The binding rate of SIgA to HK-2 (2.79%) was significantly lower than that of HRMC (81.6%) (<i>p</i> &#x3c; 0.001). The expressions of TNF-α, TGF-β1, and MCP-1 in HRMC were significantly higher than in SIgA-stimulated HK-2 (<i>p</i> &#x3c; 0.05), and their expressions were significantly higher in the SIgA-stimulated co-culture group compared with SIgA-stimulated HRMC (<i>p</i> &#x3c; 0.05). The expressions of the above cytokines were mainly detected in tubulointerstitium of IgAN patients with positive and negative SIgA deposition, without significant difference between the 2 groups, but to a significantly higher level than that in normal controls, and their expressions positively correlated with tubulointerstitial injury. <b><i>Conclusion:</i></b> Inflammatory factors released from the mesangium after SIgA deposition might mediate tubulointerstitial damage via mesangial-tubular crosstalk in IgAN.

Publisher

S. Karger AG

Subject

Cardiology and Cardiovascular Medicine,Nephrology,Cardiology and Cardiovascular Medicine,Nephrology

Reference37 articles.

1. Magistroni R, D’Agati VD, Appel GB, Kiryluk K. New developments in the genetics, pathogenesis, and therapy of IgA nephropathy. Kidney Int. 2015 Nov;88(5):974–89.

2. Wyatt RJ, Julian BA. Renal vascular lesions in IgA nephropathy. J Renal Inj Prev. 2013 Jun;2(2):37–8.

3. Suzuki H, Kiryluk K, Novak J, Moldoveanu Z, Herr AB, Renfrow MB, et al. The pathophysiology of IgA nephropathy. J Am Soc Nephrol. 2011 Oct;22(10):1795–803.

4. Oortwijn BD, van der Boog PJ, Roos A, van der Geest RN, de Fijter JW, Daha MR, et al. A pathogenic role for secretory IgA in IgA nephropathy. Kidney Int. 2006 Apr;69(7):1131–8.

5. Zhang JJ, Xu LX, Liu G, Zhao MH, Wang HY. The level of serum secretory IgA of patients with IgA nephropathy is elevated and associated with pathological phenotypes. Nephrol Dial Transplant. 2008 Jan;23(1):207–12.

Cited by 4 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3