Dual effect of chemokine CCL7/MCP-3 in the development of renal tubulointerstitial fibrosis.
Dual effect of chemokine CCL7/MCP-3 in the development of renal tubulointerstitial fibrosis.
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DOI：
10.1016/j.bbrc.2013.07.025
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发表时间：
2013-08-23
影响因子：
3.1
通讯作者：
Schanstra, Joost-Peter
中科院分区：
文献类型：
--
作者：
Gonzalez, Julien;Mouttalib, Sofia;Delage, Christine;Calise, Denis;Maoret, Jean-Jose;Pradere, Jean-Philippe;Klein, Julie;Buffin-Meyer, Benedicte;Van der Veen, Betty;Charo, Israel F.;Heeringa, Peter;Duchene, Johan;Bascands, Jean-Loup;Schanstra, Joost-Peter
大多数终末期肾病肾脏显示细胞外基质（ECM）在肾小管隔室中的积累（肾小管间质纤维化- TIF），这与将来的肾功能丧失强烈相关。虽然炎症是TIF发展中的关键事件，但它也可以具有有益的抗纤维化作用，具体取决于病理阶段。趋化因子在炎症过程中单核细胞外渗中起重要作用。CCL 2已被证明参与TIF的发展，但CCL 7是CCL 2的近亲，能够与类似的受体结合，尚未在肾脏疾病中进行研究。因此，我们在单侧输尿管梗阻（UUO）诱导的TIF模型中研究了趋化因子CCL 7。我们观察到CCL 7的作用根据病理学的阶段而不同。在早期阶段（0-8天），CCL 7缺陷（CCL 7-KO）小鼠显示出可能涉及两种机制的减弱的TIF：炎性细胞浸润的早期（0-3天）减少，随后（3-8天）是不依赖于炎症的管状ECM产生的减少。相反，在阻塞的后期阶段（10-14天），CCL 7-KO小鼠显示出增加的TIF，这再次与炎症减少相关。有趣的是，这种抗纤维化作用与促纤维化作用之间的转换伴随着免疫抑制调节性T细胞的流入增加。总之，这些结果首次强调了CCL 7在肾TIF发展中的双重作用，在早期阶段有害，但在后期阶段有益。
Most end-stage renal disease kidneys display accumulation of extracellular matrix (ECM) in the renal tubular compartment (tubular interstitial fibrosis – TIF) which is strongly correlated with the future loss of renal function. Although inflammation is a key event in the development of TIF, it can also have a beneficial anti-fibrotic role depending in particular on the stage of the pathology. Chemokines play an important role in monocyte extravasation in the inflammatory process. CCL2 has already been shown to be involved in the development of TIF but CCL7, a close relative of CCL2 and able to bind to similar receptors, has not been studied in renal disease. We therefore studied chemokine CCL7 in a model of unilateral ureteral obstruction (UUO)-induced TIF. We observed that the role of CCL7 differs depending on the stage of the pathology. In early stages (0–8 days), CCL7 deficient (CCL7-KO) mice displayed attenuated TIF potentially involving two mechanisms: an early (0–3 days) decrease of inflammatory cell infiltration followed (3–8 days) by a decrease in tubular ECM production independent of inflammation. In contrast, during later stages of obstruction (10–14 days), CCL7-KO mice displayed increased TIF which was again associated with reduced inflammation. Interestingly, the switch between this anti- to profibrotic effect was accompanied by an increased influx of immunosuppressive regulatory T cells. In conclusion, these results highlight for the first time a dual role for CCL7 in the development of renal TIF, deleterious in early stages but beneficial during later stages.
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影响因子：
3.7
作者：
Liu F;Liu J;Weng D;Chen Y;Song L;He Q;Chen J
通讯作者：
Chen J
影响因子：
6.2
作者：
Lutz, J;Yao, YS;Heemann, U
通讯作者：
Heemann, U
影响因子：
15.9
作者：
Nishida, M;Fujinaka, H;Ichikawa, I
通讯作者：
Ichikawa, I
影响因子：
6.9
作者：
Fragiadaki, Maria;Witherden, Abigail S.;Mason, Roger M.
通讯作者：
Mason, Roger M.
DOI：
10.1164/rccm.201103-0516oc
发表时间：
2011-12-01
影响因子：
24.7
作者：
Lo Re, Sandra;Lecocq, Marylene;Huaux, Francois
通讯作者：
Huaux, Francois