Basigin/CD147 Promotes Renal Fibrosis after Unilateral Ureteral Obstruction
Basigin/CD147 Promotes Renal Fibrosis after Unilateral Ureteral Obstruction
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DOI：
10.1016/j.ajpath.2010.10.009
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发表时间：
2011-02-01
影响因子：
6
通讯作者：
Kadomatsu, Kenji
中科院分区：
文献类型：
--
作者：
Kato, Noritoshi;Kosugi, Tomoki;Kadomatsu, Kenji
无论其主要原因是什么，进行性肾纤维化和肾小管萎缩是进展为终末期肾病的主要预测因素。Basigin/CD 147是一种多功能分子，例如，它诱导基质金属蛋白酶和透明质酸，并与器官纤维化有关。然而，basigin和器官纤维化之间的关系研究甚少。我们使用单侧输尿管梗阻模型研究basigin在肾纤维化中的作用。Basigin缺陷小鼠（Bsg（-/-））在手术后表现出比Bsg（+/+）小鼠显著更少的纤维化。Bsg（-/-）肾巨噬细胞浸润较少。与这些体内数据一致，来自Bsg-/-小鼠的原代培养的肾小管上皮细胞产生较少的基质金属蛋白酶，并且在用转化生长因子β刺激时表现出较少的运动性。此外，Bsg（-/-）胚胎成纤维细胞在转化生长因子13刺激后产生较少的透明质酸和α-平滑肌肌动蛋白。总之，这些结果首次证明basigin是肾纤维化的关键调节因子。Basigin可能是预防器官纤维化的候选靶分子。(Am J Pathol 2011，178：572-579; DOI：10.1016/j.ajpath.2010.10.009）
Regardless of their primary causes, progressive renal fibrosis and tubular atrophy are the main predictors of progression to end-stage renal disease. Basigin/CD147 is a multifunctional molecule-it induces matrix metalloproteinases and hyaluronan, for example-and has been implicated in organ fibrosis. However, the relationship between basigin and organ fibrosis has been poorly studied. We investigated basigin's role in renal fibrosis using a unilateral ureteral obstruction model. Basigin-deficient mice (Bsg(-/-)) demonstrated significantly less fibrosis after surgery than Bsg(+/+) mice. Fewer macrophages had infiltrated in Bsg(-/-) kidneys. Consistent with these in vivo data, primary cultured tubular epithelial cells from Bsg-/- mice produced less matrix metalloproteinase and exhibited less motility on stimulation with transforming growth factor beta. Furthermore, Bsg(-/-) embryonic fibro blasts produced less hyaluronan and a-smooth muscle actin after transforming growth factor 13 stimulation. Together, these results demonstrate for the first time that basigin is a key regulator of renal fibrosis. Basigin could be a candidate target molecule for the prevention of organ fibrosis. (Am J Pathol 2011, 178:572-579; DOI: 10.1016/j.ajpath.2010.10.009)