The role of adenosine receptors A2A and A2B signaling in renal fibrosis.
The role of adenosine receptors A2A and A2B signaling in renal fibrosis.
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DOI：
10.1038/ki.2014.244
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发表时间：
2014-10
影响因子：
19.6
通讯作者：
Veena Roberts;P. Cowan;S. Alexander;S. Robson;K. Dwyer
中科院分区：
文献类型：
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作者：
Veena Roberts;P. Cowan;S. Alexander;S. Robson;K. Dwyer
肾纤维化是慢性肾脏病（CKD）发生、发展的重要病理组织学改变，近年来成为研究的热点。CKD在发达国家和发展中国家日益加重的负担凸显了对阻止肾脏疾病进展的新疗法的需求。深入了解肾纤维化的发病机制以及关键的细胞和分子介质在确定潜在治疗靶点的过程中至关重要。腺苷信号传导是一种天然的生物自分泌和旁分泌细胞信号传导途径，涉及几种关键介质：外核苷酸酶、腺苷和腺苷受体。腺苷A2A和A2B受体的短期激活减少了炎症，这是肾纤维化的前兆。然而，在持续、过量的腺苷暴露的情况下，例如在出生时患有腺苷脱氨酶（ADA）缺乏症的患者中，通过A2B受体的腺苷信号传导促进肾纤维化，如在慢性炎症中所见。本文综述了腺苷信号在肾纤维化发展中日益被认识到的复杂作用。我们将推测所获得的知识如何用于基于这些复杂的信号通路寻找更有效的疗法。
Renal fibrosis, the key histopathological lesion in the development and progression of chronic kidney disease (CKD), has been the focus of much research in recent decades. The growing burden of CKD in both developed and developing nations highlights a need for novel therapies to halt the progression of renal disease. Insights into the pathogenesis of renal fibrosis and the key cellular and molecular mediators have been critical in the process of identifying potential targets of therapy. Adenosine signaling is an innate biological autocrine and paracrine cellular signaling pathway involving several key mediators: ectonucleotidases, adenosine, and adenosine receptors. Short-term activation of the adenosine A2Aand A2Breceptors decreases inflammation, which precedes renal fibrosis. However, in conditions of persistent, excessive adenosine exposure, such as in patients born with adenosine deaminase (ADA) deficiency, adenosine signaling via A2Breceptor promotes renal fibrosis, as seen in chronic inflammation. This review will describe the increasingly recognized complex role of adenosine signaling in the development of renal fibrosis. We will speculate how the knowledge gained may be employed in the search for more effective therapies based on these complex signaling pathways.