Renal fibrosis is an important component of chronic kidney disease, an incurable pathology with increasing prevalence worldwide. With a lack of available therapeutic options, end-stage renal disease is currently treated with renal replacement therapy through dialysis or transplantation. In recent years, many efforts have been made to identify novel targets for therapy of renal diseases, with special focus on the characterization of unknown mediators and pathways participating in renal fibrosis development. Using experimental models of renal disease and patient biopsies, we identified four novel mediators of renal fibrosis with potential to constitute future therapeutic targets against kidney disease: discoidin domain receptor 1, periostin, connexin 43, and cannabinoid receptor 1. The four candidates were highly upregulated in different models of renal disease and were localized at the sites of injury. Subsequent studies showed that they are centrally involved in the underlying mechanisms of renal fibrosis progression. Interestingly, inhibition of either of these proteins by different strategies, including gene deletion, antisense administration, or specific blockers, delayed the progression of renal disease and preserved renal structure and function, even when the inhibition started after initiation of the disease. This review will summarize the current findings on these candidates emphasizing on their potential to constitute future targets of therapy.

中文翻译：

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肾纤维化治疗的新目标。

肾纤维化是慢性肾脏疾病的重要组成部分，慢性肾脏疾病是一种无法治愈的病理，在世界范围内患病率不断上升。在缺乏可用的治疗选择的情况下，目前通过透析或移植用肾脏替代疗法治疗晚期肾病。近年来，人们为确定治疗肾脏疾病的新靶点做出了许多努力，特别着重于表征未知介质和参与肾脏纤维化发展的途径。使用肾脏疾病和患者活检的实验模型，我们确定了四种可能构成肾脏疾病未来治疗靶标的新型肾纤维化介质：盘状蛋白结构域受体1，periostin，连接蛋白43和大麻素受体1。这四种候选物在不同的肾脏疾病模型中均被高度上调，并位于损伤部位。随后的研究表明，它们主要参与了肾纤维化进展的潜在机制。有趣的是，通过不同的策略（包括基因缺失，反义给药或特异性阻滞剂）抑制这些蛋白质中的任何一种，都延迟了肾脏疾病的进展并保留了肾脏的结构和功能，即使这种抑制作用是在疾病发作后开始的。这篇综述将总结有关这些候选药物的当前发现，并强调其构成未来治疗靶标的潜力。有趣的是，通过不同的策略（包括基因缺失，反义给药或特异性阻滞剂）抑制这些蛋白质中的任何一种，都延迟了肾脏疾病的进展并保留了肾脏的结构和功能，即使这种抑制作用是在疾病发作后开始的。这篇综述将总结这些候选者的当前发现，着重介绍其潜在构成未来治疗目标的潜力。有趣的是，通过不同的策略（包括基因缺失，反义给药或特异性阻滞剂）抑制这些蛋白质中的任何一种，都延迟了肾脏疾病的进展并保留了肾脏的结构和功能，即使这种抑制作用是在疾病发作后开始的。这篇综述将总结这些候选者的当前发现，着重介绍其潜在构成未来治疗目标的潜力。