Fibroblast growth factor 1 ameliorates diabetic nephropathy by an anti-inflammatory mechanism.
Fibroblast growth factor 1 ameliorates diabetic nephropathy by an anti-inflammatory mechanism.
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成纤维细胞生长因子 1 通过抗炎机制改善糖尿病肾病
DOI：
10.1016/j.kint.2017.05.013
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发表时间：
2018-01
影响因子：
19.6
通讯作者：
Huang Z
中科院分区：
文献类型：
--
作者：
Liang G;Song L;Chen Z;Qian Y;Xie J;Zhao L;Lin Q;Zhu G;Tan Y;Li X;Mohammadi M;Huang Z
炎症在糖尿病肾病的病因中起着核心作用，糖尿病肾病是一个全球性的健康问题。我们在糖尿病肾病患者和小鼠模型中观察到成纤维细胞生长因子1的表达显著减少，成纤维细胞生长因子1是一种已知的有丝分裂原和胰岛素增敏剂，这意味着成纤维细胞生长因子1在体内具有有益的抗炎和肾脏保护活性。为了验证这一可能性，我们研究了在链脲佐菌素诱导的1型糖尿病模型和db/db 2型糖尿病模型中长期给予成纤维细胞生长因子1的效果。事实上，重组成纤维细胞生长因子1显著抑制了1型和2型糖尿病小鼠的肾炎症(即细胞因子、巨噬细胞浸润)、肾小球和肾小管损伤以及肾功能障碍。成纤维细胞生长因子1能纠正2型糖尿病小鼠的血糖升高，但不能纠正1型糖尿病小鼠的血糖升高，提示成纤维细胞生长因子1的抗炎作用不依赖于其降糖活性。该机制研究表明，成纤维细胞生长因子1在体内抑制肾脏炎症的同时伴随着核因子κB和c-jun氨基末端激酶信号通路的减弱，进一步在体外用培养的肾小球系膜细胞和足细胞进行了验证。因此，成纤维细胞生长因子1通过对抗受损肾组织中的炎症信号级联反应，为开发糖尿病肾病的新治疗方法提供了巨大的希望。
Inflammation plays a central role in the etiology of diabetic nephropathy, a global health issue. We observed a significant reduction in the renal expression of fibroblast growth factor 1, a known mitogen and insulin sensitizer, in patients with diabetic nephropathy and in mouse models implying that fibroblast growth factor 1 possesses beneficial anti-inflammatory and renoprotective activities in vivo. To test this possibility, we investigated the effects of chronic intraperitoneal administration of fibroblast growth factor 1 into both the streptozotocin-induced type 1 diabetes and db/db type 2 diabetes models. Indeed, recombinant fibroblast growth factor 1 significantly suppressed renal inflammation (i.e., cytokines, macrophage infiltration), glomerular and tubular damage, and renal dysfunction in both type 1 and type 2 diabetes mice. Fibroblast growth factor 1 was able to correct the elevated blood glucose levels in type 2 but not in type 1 diabetic mice, suggesting that the anti-inflammatory effect of fibroblast growth factor 1 was independent of its glucose-lowering activity. The mechanistic study demonstrated that fibroblast growth factor 1–mediated inhibition of the renal inflammation in vivo was accompanied by attenuation of the nuclear factor κB and c-Jun N-terminal kinase signaling pathways, further validated in vitro using cultured glomerular mesangial cells and podocytes. Thus, fibroblast growth factor 1 holds great promise for developing new treatments for diabetic nephropathy through countering inflammatory signaling cascades in injured renal tissue.
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影响因子：
4.4
作者：
Båge T;Lindberg J;Lundeberg J;Modéer T;Yucel-Lindberg T
通讯作者：
Yucel-Lindberg T
影响因子：
19.6
作者：
Kang, Young Sun;Lee, Mi Hwa;Cha, Dae Ryong
通讯作者：
Cha, Dae Ryong
影响因子：
13.6
作者：
Ma, Frank Y.;Flanc, Robert S.;Nikolic-Paterson, David J.
通讯作者：
Nikolic-Paterson, David J.
影响因子：
16.6
作者：
Perry, Rachel J.;Lee, Sangwon;Ma, Lie;Zhang, Dongyan;Schlessinger, Joseph;Shulman, Gerald I.
通讯作者：
Shulman, Gerald I.
DOI：
10.1126/science.1227568
发表时间：
2013-01-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Han MS;Jung DY;Morel C;Lakhani SA;Kim JK;Flavell RA;Davis RJ
通讯作者：
Davis RJ