C-reactive protein exacerbates epithelial-mesenchymal transition through Wnt/-catenin and ERK signaling in streptozocin-induced diabetic nephropathy
C-reactive protein exacerbates epithelial-mesenchymal transition through Wnt/-catenin and ERK signaling in streptozocin-induced diabetic nephropathy
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C反应蛋白通过Wnt/-catenin和ERK信号在链佐星诱导的糖尿病肾病中加剧上皮-间质转化
DOI：
10.1096/fj.201801865rr
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Ji Shang Rong
中科院分区：
文献类型：
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作者：
Zhang Lin;Shen Zhi Yuan;Wang Ke;Li Wei;Shi Jing Ming;Osoro Ezra Kombo;Ullah Naeem;Zhou Yan;Ji Shang Rong
先前的研究报道了C反应蛋白（CRP）在人转基因和CRP - / -小鼠糖尿病肾病（DKD）中的致病作用。然而，由于人类和小鼠具有CRP和血清淀粉样蛋白P成分的逆急性期表达模式，这可能导致上述CRP转基因小鼠对CRP功能的评估不准确。但与小鼠不同的是，大鼠具有与人类相同的急性期蛋白表达模式，这可能会避免这一问题，成为CRP功能研究的更好选择。为了消除这一疑问并准确定义CRP在糖尿病肾病中的作用，我们创建了第一个CRP - / -大鼠模型，我们用链脲佐菌素治疗以诱导DKD进行体内研究。此外，我们利用已建立的细胞系（人肾2）来进一步研究CRP的病理机制。我们发现CRP通过Wnt/β‐catenin和ERK1/2信号通路促进上皮-间充质转化（EMT），这些信号通路依赖于CRP与凋亡细胞fc - γ rii的结合。通过促进EMT， CRP被证明可以加速DKD的发展。因此，我们提出了令人信服的证据，证明CRP是DKD治疗的治疗靶点（zhang， L, Shen, z - Y）。王凯，李伟，石建民。，周永强，周永强，周永强，季永强。在链脲佐菌素诱导的糖尿病肾病中，C反应蛋白通过Wnt/β -连环蛋白和ERK信号通路加剧了上皮-间质转化。中国生物医学工程学报，2016,32(2):481 - 481。www.fasebj.org
Previous studies have reported the pathogenic role of C‐reactive protein (CRP) during diabetic kidney disease (DKD) in humanCRPtransgenic andCrp−/−mice. However, because humans and mice have inverse acute phase expression patterns of CRP and serum amyloid P component, this could lead to the inaccurate evaluation of CRP function with the above‐mentioned CRP transgenic mouse. But different from mice, rats have the same acute phase protein expression pattern as human, which might avoid this problem and be a better choice for CRP function studies. To dispel this doubt and accurately define the role of CRP during diabetic nephropathy, we created the firstCrp−/−rat model, which we treated with streptozocin to induce DKD forin vivostudies. Moreover, an established cell line (human kidney 2) was used to further investigate the pathologic mechanisms of CRP. We found that CRP promotes epimelial‐mesenchymal transition (EMT) through Wnt/β‐catenin and ERK1/2 signaling, which are dependent on CRP binding to FcγRII on apoptotic cells. By promoting EMT, CRP was demonstrated to accelerate the development of DKD. We thus present convincing evidence demonstrating CRP as a therapeutic target for DKD treatment—Zhang, L., Shen, Z.‐Y., Wang, K., Li, W., Shi, J.‐M., Osoro, E. K., Ullah, N., Zhou, Y., Ji, S.‐R. C‐reactive protein exacerbates epimelial‐mesenchymal transition through Wnt/β‐catenin and ERK signaling in streptozocin‐induced diabetic nephropathy. FASEB J. 33, 6551–6563 (2019). www.fasebj.org