IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy.
IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy.
Pharmacol Res. 2016 Jun;108:16-22. doi: 10.1016/j.phrs.2016.04.009. Epub 2016 Apr 16.
Independently of the initial insult, activation and accumulation of parietal progenitor cells within the Bowman's space is a peculiar feature of proliferative chronic kidney diseases. Clinical and experimental studies demonstrated that, in the presence of extensive renal damage, progenitor cells proliferate excessively in the failed attempt to replace the injured podocytes, contributing to the development of crescentic lesions. Inhibiting angiotensin-converting enzyme (ACE) halts crescent formation and promotes the restoration of normal glomerular architecture by limiting progenitor cell proliferation and migration towards the glomerular tuft. Among the mediators involved in the dysregulated response of renal precursors, the angiotensin II (ang II)/ang II type-1 (AT) receptor/CXCR4 pathway have been demonstrated to be crucial in proliferative diseases. Understanding the mechanisms underlying the formation of crescentic lesions could be instrumental to developing new therapies, which can be more effective and more targeted to molecular mediators than the currently used cytotoxic agents.
无论最初的损伤如何，在鲍曼氏囊内，顶泌细胞的激活和累积是增殖性慢性肾脏病的一个特征。临床和实验研究表明，在广泛的肾损伤存在的情况下，祖细胞过度增殖，试图替代受损的足细胞，但这反而导致新月体病变的发生。抑制血管紧张素转换酶 (ACE) 可阻止新月体形成，并通过限制祖细胞增殖和向肾小球丛迁移来促进正常肾小球结构的恢复。在肾前体细胞失调反应中涉及的介质中，血管紧张素 II (ang II)/ang II 型 1 (AT) 受体/CXCR4 途径已被证明在增殖性疾病中至关重要。了解新月体病变形成的机制对于开发新的治疗方法非常重要，这些方法可能比目前使用的细胞毒性药物更有效、更针对分子介质。
