Impact of heparanase on renal fibrosis.
Impact of heparanase on renal fibrosis.
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DOI：
10.1186/s12967-015-0538-5
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发表时间：
2015-06-04
影响因子：
7.4
通讯作者：
Gambaro G
中科院分区：
文献类型：
--
作者：
Masola V;Zaza G;Onisto M;Lupo A;Gambaro G
肾小管间质纤维化已被认为是慢性肾脏疾病进展的标志，但是，尽管进行了大量的研究，目前还没有针对这种疾病的生物标志物或有效的治疗方法。在此背景下，一个有希望的候选者可能是乙酰肝素酶-1(HPSE)，一种内切糖苷酶，它能裂解硫酸乙酰肝素链，从而参与细胞外基质重塑。正如大部分描述的那样，它在癌症和炎症的发病机制中发挥核心作用，并参与不同肾脏蛋白尿疾病(如糖尿病肾病、肾小球肾炎)的发病的复杂生物机制。此外，HPSE可能通过其在肾脏纤维化的生物学途径中的主要作用而显著影响慢性肾损害的进展。在这里，我们简要总结支持HPSE在肾脏损伤中的作用的数据，重点关注最近的证据表明该酶能够调节促纤维化因子如成纤维细胞生长因子-2和转化生长因子-β的信号转导，从而控制肾小管上皮细胞-间充质细胞的转变。我们还强调，研究界需要进行研究和临床试验，以评估这种酶作为诊断和预后工具的潜在临床应用和/或作为新的药物干预的治疗靶点的作用。
Tubulo-interstitial fibrosis has been recognized as the hallmark of progression of chronic kidney disease, but, despite intensive research studies, there are currently no biomarkers or effective treatments for this condition. In this context, a promising candidate could be heparanase-1 (HPSE), an endoglycosidase that cleaves heparan sulfate chains and thus takes part in extracellular matrix remodeling. As largely described, it has a central role in the pathogenesis of cancer and inflammation, and it participates in the complex biological machinery involved in the onset of different renal proteinuric diseases (e.g., diabetic nephropathy, glomerulonephritis). Additionally, HPSE may significantly influence the progression of chronic kidney damage trough its major role in the biological pathway of renal fibrogenesis. Here, we briefly summarize data supporting the role of HPSE in renal damage, focusing on recent evidences that demonstrate the capability of this enzyme to modulate the signaling of pro-fibrotic factors such as FGF-2 and TGF-β and consequently to control the epithelial-mesenchymal transition in renal tubular cells. We also emphasize the need of the research community to undertake studies and clinical trials to assess the potential clinical employment of this enzyme as diagnostic and prognostic tool and/or its role as therapeutic target for new pharmacological interventions.
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影响因子：
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作者：
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DOI：
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发表时间：
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影响因子：
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