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ALW peptide ameliorates lupus nephritis in MRL/lpr mice.
Arthritis Research & Therapy ( IF 4.9 ) Pub Date : 2019-12-02 , DOI: 10.1186/s13075-019-2038-0
Huixia Wang 1 , Mei Lu 1 , Siyue Zhai 1 , Kunyi Wu 2 , Lingling Peng 1 , Jie Yang 3 , Yumin Xia 1
Affiliation  

Lupus nephritis (LN) is a common and serious complication of systemic lupus erythematosus. Anti-double-stranded (ds) DNA immunoglobulin G (IgG) plays a pivotal role in the pathogenesis of LN. Currently, there are various therapies for patients with LN; however, most of them are associated with considerable side effects. We confirmed previously that ALW (ALWPPNLHAWVP), a 12-amino acid peptide, inhibited the binding of polyclonal anti-dsDNA antibodies to mesangial cells and isolated glomeruli in vitro. In this study, we further investigate whether the administration of ALW peptide decreases renal IgG deposition and relevant damage in MRL/lpr lupus-prone mice. Forty female MRL/lpr mice were randomly divided into four groups. The mice were intravenously injected with D-form ALW peptide (ALW group), scrambled peptide (PLP group), and normal saline (NaCl group) or were not treated (blank group). The IgG deposition, the histopathologic changes, and the expressions of profibrotic factors were analyzed in the kidney of MRL/lpr mice. Compared with the other groups, glomerular deposition of IgG, IgG2a, IgG2b, and IgG3 was decreased in the ALW group. Moreover, ALW administration attenuated renal histopathologic changes in MRL/lpr mice, including mesangial proliferation and infiltration of inflammatory cells. Furthermore, the expressions of profibrotic cytokines, such as transforming growth factor-beta1 (TGF-β1) and platelet-derived growth factor B (PDGF-B), decreased in the serum and kidney tissue of ALW-treated mice. Our study demonstrated that ALW peptide ameliorates the murine model of LN, possibly through inhibiting renal IgG deposition and relevant tissue inflammation and fibrosis.

中文翻译:

ALW肽改善了MRL / lpr小鼠的狼疮肾炎。

狼疮性肾炎(LN)是系统性红斑狼疮的常见和严重并发症。抗双链(ds)DNA免疫球蛋白G(IgG)在LN的发病机理中起着关键作用。当前,有许多针对LN患者的疗法。然而,它们大多数与相当大的副作用有关。我们先前确认,ALW(ALWPPNLHAWVP),一种12个氨基酸的肽,在体外抑制多克隆抗dsDNA抗体与系膜细胞和分离的肾小球的结合。在这项研究中,我们进一步研究了ALW肽的施用是否会降低MRL / lpr狼疮易感小鼠的肾脏IgG沉积和相关损伤。40只MRL / lpr雌性小鼠随机分为四组。给小鼠静脉注射D型ALW肽(ALW组),加扰肽(PLP组),和生理盐水(NaCl组)或未治疗(空白组)。分析了MRL / lpr小鼠肾脏中的IgG沉积,组织病理学变化和纤维化因子的表达。与其他组相比,ALW组的IgG,IgG2a,IgG2b和IgG3的肾小球沉积减少。此外,ALW给药减弱了MRL / lpr小鼠的肾脏组织病理学变化,包括肾小球膜增生和炎性细胞浸润。此外,ALW处理的小鼠的血清和肾脏组织中,诸如转化生长因子β1(TGF-β1)和血小板衍生生长因子B(PDGF-B)之类的原纤维化细胞因子的表达降低。我们的研究表明,ALW肽改善了LN的小鼠模型,
更新日期:2019-12-02
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