Department of Biochemistry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Am J Pathol. 2011 Feb;178(2):572-9. 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 β. Furthermore, Bsg(-/-) embryonic fibro blasts produced less hyaluronan and α-smooth muscle actin after transforming growth factor β 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.
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/CD147 是一种多功能分子——例如，它能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 与器官纤维化之间的关系还研究得很少。我们使用单侧输尿管梗阻模型研究了 Basigin 在肾纤维化中的作用。与 Bsg(+/+) 小鼠相比，Basigin 缺陷型（Bsg(-/-)）小鼠手术后的纤维化明显减少。Bsg(-/-) 肾脏中的巨噬细胞浸润较少。与这些体内数据一致，从小鼠原代培养的肾小管上皮细胞中分离出的细胞在受到转化生长因子 β 刺激时产生的基质金属蛋白酶较少，运动性也较差。此外，Bsg(-/-) 胚胎成纤维细胞在受到转化生长因子 β 刺激后产生的透明质酸和α-平滑肌肌动蛋白较少。总之，这些结果首次表明 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。
