ALW peptide ameliorates lupus nephritis in MRL/lpr mice
ALW peptide ameliorates lupus nephritis in MRL/lpr mice
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ALW 肽可改善 MRL/lpr 小鼠狼疮性肾炎
DOI：
10.1186/s13075-019-2038-0
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发表时间：
2019-12-02
影响因子：
4.9
通讯作者：
Xia, Yumin
中科院分区：
文献类型：
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作者：
Wang, Huixia;Lu, Mei;Xia, Yumin
狼疮性肾炎（LN）是系统性红斑狼疮常见而严重的并发症.抗双链DNA免疫球蛋白G（IgG）在LN的发病机制中起关键作用。目前，LN患者有各种治疗方法;然而，其中大多数与相当大的副作用有关。我们以前证实，ALW（ALWPPNLHAWVP），一个12个氨基酸的肽，抑制多克隆抗dsDNA抗体的系膜细胞和分离的肾小球在体外的结合。在这项研究中，我们进一步调查是否ALW肽的管理减少肾IgG沉积和相关的损害MRL/lpr lupus-prone.MethodsForty雌性MRL/lpr小鼠随机分为四组。给小鼠静脉注射D型ALW肽（ALW组）、乱序肽（PLP组）和生理盐水（NaCl组）或不给药（空白组）。结果与其他各组相比，ALW组肾小球IgG、IgG 2a、IgG 2b和IgG 3沉积减少，肾脏组织病理学改变减轻，肾小球纤维化因子表达减少。此外，ALW给药减轻了MRL/lpr小鼠的肾脏组织病理学变化，包括系膜增生和炎性细胞浸润。此外，促纤维化的细胞因子，如转化生长因子-β 1（TGF-β1）和血小板衍生生长因子B（PDGF-B）的表达，ALW-治疗mice.ConclusionsOur研究表明，ALW肽改善LN的小鼠模型，可能通过抑制肾脏IgG沉积和相关组织炎症和纤维化。
BackgroundLupus 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.MethodsForty 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.ResultsCompared 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.ConclusionsOur study demonstrated that ALW peptide ameliorates the murine model of LN, possibly through inhibiting renal IgG deposition and relevant tissue inflammation and fibrosis.