Pharmazentrum frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main, Germany.
J Biomed Sci. 2010 Jan 13;17(1):3. doi: 10.1186/1423-0127-17-3.
The importance of the Notch signaling in the development of glomerular diseases has been recently described. Therefore we analyzed in podocytes the expression and activity of ADAM10, one important component of the Notch signaling complex.
By Western blot, immunofluorescence and immunohistochemistry analysis we characterized the expression of ADAM10 in human podocytes, human urine and human renal tissue.
We present evidence, that differentiated human podocytes possessed increased amounts of mature ADAM10 and released elevated levels of L1 adhesion molecule, one well known substrate of ADAM10. By using specific siRNA and metalloproteinase inhibitors we demonstrate that ADAM10 is involved in the cleavage of L1 in human podocytes. Injury of podocytes enhanced the ADAM10 mediated cleavage of L1. In addition, we detected ADAM10 in urinary podocytes from patients with kidney diseases and in tissue sections of normal human kidney. Finally, we found elevated levels of ADAM10 in urinary vesicles of patients with glomerular kidney diseases.
The activity of ADAM10 in human podocytes may play an important role in the development of glomerular kidney diseases.
Notch 信号在肾小球疾病的发展中的重要性最近已经被描述。因此，我们分析了足细胞中 Notch 信号复合物的一个重要组成部分 ADAM10 的表达和活性。
通过 Western blot、免疫荧光和免疫组织化学分析，我们对人足细胞、人尿和人肾组织中 ADAM10 的表达进行了特征分析。
我们提供了证据，表明分化的人足细胞具有增加的成熟 ADAM10 量，并释放出更高水平的 L1 粘附分子，这是 ADAM10 的一个众所周知的底物。通过使用特异性 siRNA 和金属蛋白酶抑制剂，我们证明 ADAM10 参与了人足细胞中 L1 的切割。足细胞的损伤增强了 ADAM10 介导的 L1 切割。此外，我们在肾脏病患者的尿足细胞和正常人类肾脏组织切片中检测到了 ADAM10。最后，我们发现肾小球肾脏病患者的尿囊泡中 ADAM10 水平升高。
ADAM10 在人足细胞中的活性可能在肾小球肾脏病的发展中发挥重要作用。
Zotero 插件
