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IgA 聚集体对人系膜细胞中转化生长因子-β1 产生的影响以及 IgA 肾病患者肾小球内转化生长因子-β1 的表达

Effect of IgA aggregates on transforming growth factor-beta1 production in human mesangial cells and the intraglomerular expression of transforming growth factor-beta1 in patients with IgA nephropathy.

作者信息

Han Sang-Youb, Ihm Chun-Gyoo, Cha Dae-Ryong, Kang Young-Sun, Han Kum-Hyun, Kim Hyoung-Kyu, Han Jee-Young

机构信息

Department of Internal Medicine, Inje University College of Medicine, Go-yang, Korea.

出版信息

Korean J Intern Med. 2005 Mar;20(1):40-7. doi: 10.3904/kjim.2005.20.1.40.

DOI:10.3904/kjim.2005.20.1.40
PMID:15906952
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3891411/
Abstract

BACKGROUND

Transforming growth factor-beta (TGF-beta) stimulates renal fibrosis in various renal diseases including IgA nephropathy.

METHODS

We examined whether immunoglobulin A (IgA) stimulated TGF-beta1 synthesis in human mesangial cells (MCs), and whether this effect was mediated through the protein kinase C (PKC) pathway. We measured the intraglomerular TGF-beta1 mRNA expression by using competitive RT-PCR, and this was compared with various parameters in IgA nephropathy patients.

RESULTS

The IgA aggregate increased the TGF-beta1 mRNA expression in MCs, while this expression was not affected by the culture media or IgG aggregate. Phorbol 12-myristate 13-acetate and calphostin C did not influence the TGF-beta1 mRNA expression that was increased by the IgA aggregate. Intraglomerular TGF-beta1 mRNA expression was significantly correlated with creatinine clearance (r = -0.764, p = 0.027), daily proteinuria (r = 0.781, p = 0.022), serum creatinine (r = 0.884, p = 0.004), and tubulointerstitial changes (r = 0.809, p = 0.015). Glomerular TGF-beta1 mRNA expression was associated with an increased tendency for glomerulosclerosis (r = 0.646, p = 0.084). After 4 years, patients with a high expression of intraglomerular TGF-beta1 mRNA showed a tendency for an decrease of their renal function.

CONCLUSION

The IgA aggregate increased TGF-beta1 mRNA expression in MCs, and this was independent of the PKC pathway. The evaluation of intraglomerular TGF-beta1 mRNA expression could be useful in predicting the progression of IgA nephropathy.

摘要

背景

转化生长因子-β（TGF-β）在包括IgA肾病在内的各种肾脏疾病中可刺激肾纤维化。

方法

我们研究了免疫球蛋白A（IgA）是否刺激人系膜细胞（MCs）中TGF-β1的合成，以及这种效应是否通过蛋白激酶C（PKC）途径介导。我们使用竞争性逆转录聚合酶链反应（RT-PCR）测量肾小球内TGF-β1 mRNA表达，并将其与IgA肾病患者的各种参数进行比较。

结果

IgA聚集体增加了MCs中TGF-β1 mRNA表达，而这种表达不受培养基或IgG聚集体的影响。佛波酯12-肉豆蔻酸酯13-乙酸酯和钙泊三醇C不影响由IgA聚集体增加的TGF-β1 mRNA表达。肾小球内TGF-β1 mRNA表达与肌酐清除率显著相关（r = -0.764，p = 0.027）、每日蛋白尿（r = 0.781，p = 0.022）、血清肌酐（r = 0.884，p = 0.004）以及肾小管间质变化（r = 0.809，p = 0.015）。肾小球TGF-β1 mRNA表达与肾小球硬化的增加趋势相关（r = 0.646，p = 0.084）。4年后，肾小球内TGF-β1 mRNA高表达的患者显示出肾功能下降的趋势。

结论

IgA聚集体增加了MCs中TGF-β1 mRNA表达，且这一过程独立于PKC途径。评估肾小球内TGF-β1 mRNA表达可能有助于预测IgA肾病的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d312/3891411/c5cad01af131/kjim-20-40-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d312/3891411/daf5a53255cc/kjim-20-40-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d312/3891411/b042322628d2/kjim-20-40-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d312/3891411/8104749eb9fa/kjim-20-40-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d312/3891411/4d8a5dea8898/kjim-20-40-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d312/3891411/c5cad01af131/kjim-20-40-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d312/3891411/daf5a53255cc/kjim-20-40-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d312/3891411/b042322628d2/kjim-20-40-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d312/3891411/8104749eb9fa/kjim-20-40-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d312/3891411/4d8a5dea8898/kjim-20-40-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d312/3891411/c5cad01af131/kjim-20-40-g005.jpg

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