Annexin A1 alleviates kidney injury by promoting the resolution of inflammation in diabetic nephropathy.
Annexin A1 alleviates kidney injury by promoting the resolution of inflammation in diabetic nephropathy.
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膜联蛋白 A1 通过促进糖尿病肾病炎症消退来减轻肾损伤
DOI：
10.1016/j.kint.2021.02.025
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发表时间：
2021-07
影响因子：
19.6
通讯作者：
Zheng L
中科院分区：
文献类型：
--
作者：
Wu L;Liu C;Chang DY;Zhan R;Sun J;Cui SH;Eddy S;Nair V;Tanner E;Brosius FC;Looker HC;Nelson RG;Kretzler M;Wang JC;Xu M;Ju W;Zhao MH;Chen M;Zheng L
由于炎症消退失败是糖尿病肾病进展的主要原因，因此鉴定促进炎症生理消退的内源性产生的分子可能是这种疾病的有希望的治疗方法。膜联蛋白A1（Annexin A1，ANXA 1）作为一种内源性介质，在炎症反应中起重要作用。ANXA 1是否可以通过调节炎症状态影响已建立的糖尿病肾病仍然是未知的。在目前的研究中，我们发现在糖尿病肾病患者中，ANXA 1水平在肾脏中上调，并与肾功能以及肾脏结局相关。因此，进一步评估内源性ANXA 1在糖尿病肾病小鼠模型中的作用。ANXA 1缺乏加重了肾损伤，在高脂饮食/链脲佐菌素诱导的糖尿病小鼠中表现出更严重的蛋白尿、系膜基质扩张、肾小管间质病变、肾脏炎症和纤维化。因此，ANXA 1过表达可改善糖尿病肾病小鼠的肾损伤。此外，我们发现Ac 2 -26（一种ANXA 1模拟肽）具有减轻db/db小鼠和糖尿病Anxa 1敲除小鼠肾脏损伤的治疗潜力。机制研究表明，细胞内ANXA 1与转录因子NF-κB p65亚基结合，抑制其活化，从而调节炎症状态。因此，我们的数据表明ANXA 1可能是治疗和逆转糖尿病肾病的一种有前途的治疗方法。
Since failed resolution of inflammation is a major contributor to the progression of diabetic nephropathy, identifying endogenously generated molecules that promote the physiological resolution of inflammation may be a promising therapeutic approach for this disease. Annexin A1 (ANXA1), as an endogenous mediator, plays an important role in resolving inflammation. Whether ANXA1 could affect established diabetic nephropathy through modulating inflammatory states remains largely unknown. In the current study, we found that in patients with diabetic nephropathy, the levels of ANXA1 were upregulated in kidneys, and correlated with kidney function as well as kidney outcomes. Therefore, the role of endogenous ANXA1 in mouse models of diabetic nephropathy was further evaluated. ANXA1 deficiency exacerbated kidney injuries, exhibiting more severe albuminuria, mesangial matrix expansion, tubulointerstitial lesions, kidney inflammation and fibrosis in high fat diet/streptozotocin-induced-diabetic mice. Consistently, ANXA1 overexpression ameliorated kidney injuries in mice with diabetic nephropathy. Additionally, we found Ac2-26 (an ANXA1 mimetic peptide) had therapeutic potential for alleviating kidney injuries in db/db mice and diabetic Anxa1 knockout mice. Mechanistic studies demonstrated that intracellular ANXA1 bound to the transcription factor NF-κB p65 subunit, inhibiting its activation thereby modulating the inflammatory state. Thus, our data indicate that ANXA1 may be a promising therapeutic approach to treating and reversing diabetic nephropathy.
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影响因子：
8.2
作者：
Purvis GSD;Chiazza F;Chen J;Azevedo-Loiola R;Martin L;Kusters DHM;Reutelingsperger C;Fountoulakis N;Gnudi L;Yaqoob MM;Collino M;Thiemermann C;Solito E
通讯作者：
Solito E
影响因子：
19.6
作者：
Kelly, DJ;Wilkinson-Berka, JL;Skinner, SL
通讯作者：
Skinner, SL
DOI：
10.1073/pnas.1218620110
发表时间：
2013-03-26
影响因子：
11.1
作者：
Li, Zhijie;Michael, Iacovos P.;Rini, James M.
通讯作者：
Rini, James M.
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影响因子：
13.6
作者：
Wu, Peiwen;Wang, Yanxia;Ma, Rong
通讯作者：
Ma, Rong
影响因子：
15.1
作者：
Li, Chenwen;Zhao, Yang;Zhang, Jianxiang
通讯作者：
Zhang, Jianxiang