Ghrelin attenuates renal fibrosis and inflammation of obstructive nephropathy.
Ghrelin attenuates renal fibrosis and inflammation of obstructive nephropathy.
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DOI：
10.1016/j.juro.2014.11.098
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发表时间：
2015-06
期刊：
影响因子：
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通讯作者：
Guang-Xi Sun;Rui Ding;Ming Li;Ying Guo;Li-pei Fan;Liang-sheng Yue;Liu-yang Li;Ming Zhao
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文献类型：
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作者：
Guang-Xi Sun;Rui Ding;Ming Li;Ying Guo;Li-pei Fan;Liang-sheng Yue;Liu-yang Li;Ming Zhao
目的Ghrelin是一种调节多种生物学功能的胃肽，其中刺激食物摄入是最著名的功能。Ghrelin还在不同器官中发挥潜在的抗炎和抗纤维化特性，但据我们所知，Ghrelin是否抑制肾纤维化的进展尚不清楚。因此，我们研究了生长素释放肽在大鼠肾纤维化模型中的作用和潜在机制。材料和方法雄性Sprague道利大鼠分为4组，包括载体或生长素释放肽处理的假手术组和载体或生长素释放肽处理的单侧输尿管梗阻组。肾脏收获术后第7天或14天进行了评价肾脏炎症，纤维化和细胞凋亡，和表达的促纤维化和促炎factors.ResultsGhrelin抑制肾纤维化衰减胶原蛋白的产生，细胞外基质沉积，α-平滑肌肌动蛋白和纤连蛋白的表达。Ghrelin给药减少了巨噬细胞浸润和几种促炎细胞因子，包括肿瘤坏死因子-α、白细胞介素-1 β和单核细胞趋化蛋白-1，以及磷酸化核因子-κB p65。Ghrelin还通过阻断转化生长因子-β1/Smad 3信号通路抑制肌成纤维细胞聚集。此外，ghrelin衰减肾小管细胞凋亡和上皮间质转化过程中诱导的单侧输尿管梗阻injure.ConclusionsThese研究结果表明，ghrelin是一种有效的抗纤维化剂，可能有治疗潜力的梗阻性肾病患者。
PurposeGhrelin is a gastric peptide that modulates multiple biological functions, of which the stimulation of food intake is the most well-known function. Ghrelin also exerts potential anti-inflammatory and antifibrotic properties in different organs but to our knowledge whether ghrelin inhibits the progression of renal fibrosis is unknown. Thus, we investigated the effect and underlying mechanisms of ghrelin in a rat model of renal fibrosis.Materials and MethodsMale Sprague Dawley® rats were divided into 4 groups, including vehicle or ghrelin treated sham operated groups and vehicle or ghrelin treated unilateral ureteral obstruction groups. Kidneys harvested on postoperative day 7 or 14 were evaluated for renal inflammation, fibrosis and apoptosis, and the expression of profibrotic and proinflammatory factors.ResultsGhrelin inhibited renal fibrosis by attenuating collagen production, extracellular matrix deposition, and α-smooth muscle actin and fibronectin expression. Ghrelin administration decreased macrophage infiltration and several proinflammatory cytokines, including tumor necrosis factor-α, interleukin-1β and monocyte chemotactic protein-1, as well as phosphorylated nuclear factor-κB p65. Ghrelin also inhibited myofibroblast accumulation by blocking the transforming growth factor-β1/Smad3 signaling pathway. Furthermore, ghrelin attenuated renal tubular cell apoptosis and epithelial-mesenchymal transition processes induced by unilateral ureteral obstruction injury.ConclusionsThese findings indicate that ghrelin is a potent antifibrotic agent that may have therapeutic potential in patients with obstructive nephropathy.