JASN:巨噬细胞-成肌纤维细胞转换导致慢性移植肾损伤的间质纤维化

2017-07-20 xuyihan MedSci原创

众所周知间质纤维化是慢性肾移植术后失败的重要原因。目前已知炎性巨噬细胞与移植肾的纤维化有关,但是这些细胞如何导致这种损伤反应的机制尚未明了。2017年7月在JASN上发表的一篇文章研究了巨噬细胞-成肌纤维细胞转变在人类和实验性慢性移植肾损伤的肾间质纤维化中所扮演的角色。

众所周知间质纤维化是慢性肾移植术后失败的重要原因。目前已知炎性巨噬细胞与移植肾的纤维化有关,但是这些细胞如何导致这种损伤反应的机制尚未明了。2017年7月在JASN上发表的一篇文章研究了巨噬细胞-成肌纤维细胞转变在人类和实验性慢性移植肾损伤的肾间质纤维化中所扮演的角色。

该研究在出现慢性移植物排斥反应患者的活检标本中,通过巨噬细胞(CD68)和成肌纤维细胞(α-平滑肌肌动蛋白[α-SMA])标记物的共表达,发现细胞经历了由巨噬细胞到成肌纤维细胞的转化。CD68+/α-SMA+细胞占约集成纤维细胞的50%,这些细胞与移植肾功能和肾间质纤维化的严重程度相关。同样的,在有BALB/c移植肾的C57BL/6J小鼠中,共表达巨噬细胞标记物(CD68或F4/80)和α-SMA的细胞占据了发生慢性移植物排斥反应的肾间质的大多数。

在LYZ2 Cre/ROSA26小鼠中,表明移植肾中大约一半的α-SMA+肌成纤维细胞来自于受体骨髓来源的巨噬细胞。敲除Smad3可以防止移植肾间质纤维化和大幅度减少巨噬细胞-肌成纤维细胞转变的数量。除此之外,在人类和实验性移植肾排斥中出现的巨噬细胞-肌成纤维细胞转变的细胞大多数共表达M2型巨噬细胞标记物CD206,而这种表达在敲除Smad3的受体中明显减少。

由此可见,该项研究表明巨噬细胞-肌成纤维细胞转变导致了慢性移植肾损伤的肾间质纤维化。此外,骨髓来源的M2型巨噬细胞到肌成纤维细胞的转变是通过Smad3基因调控的。

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    2018-05-11 chenhongpeng
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    2017-11-17 okhuali
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