Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, China.
Eur Rev Med Pharmacol Sci. 2019 Jan;23(2):755-763. doi: 10.26355/eurrev_201901_16890.
Yes-associated protein (YAP) is a critical factor of Hippo pathway. It can control organ size, regulate proliferation, differentiation, and apoptosis of cells, and mediate epithelial-mesenchymal transition and cell contact inhibition. It has gradually become a hot spot in the field of diabetic nephropathy (DN). Tea domain (TEAD) is a factor with a deoxyribose nucleic acid (DNA) binding domain, which combines with activated YAP to control the expression of their important target factor - connective tissue growth factor (CTGF).
We have investigated the role of YAP in type 2 diabetic nephropathy and evaluated the correlation between YAP and the progress of type 2 diabetic nephropathy. We have detected the expression of YAP, TEAD and CTGF in normal people (n=10) and patients with DN (n=51) by immunohistochemical and immunofluorescence staining and evaluated the relationship among clinical, pathologic data and YAP expression in type 2 diabetic nephropathy.
In kidneys of type 2 diabetic nephropathy, YAP, TEAD and CTGF were highly expressed in the nucleus of glomerular podocytes. In those healthy kidneys, however, all three of the above factors were mainly expressed in cytoplasm. Furthermore, the high expression of YAP in DN had relevance to increasing systolic blood pressure (SBP) (r=0.484, p=0.019), blood urea nitrogen (BUN) (r=0.522, p=0.032), creatinine (Cr) (r=0.496, p=0.031), progression of DN stage (r=0.647, p=0.001) and progression of DN pathologic classification (r=0.298, p=0.033). In addition, decreasing serum albumin (SAlb) (r=-0.656, p=0.001) and estimated glomerular filtration rate (eGFR) (r=-0.607, p=0.006) were also correlated with the high expression of YAP in DN.
High expression of YAP, TEAD and CTGF in kidney tissues suggested that YAP played a significant role in the renal damage of type 2 diabetic nephropathy. YAP that is correlated with SBP, BUN, Cr, DN stage, DN pathologic classification, SAlb and eGFR, suggested that inhibition of the activity of YAP might have the effect in delaying DN progression.
Yes 相关蛋白（YAP）是 Hippo 通路的关键因子。它可以控制器官大小，调节细胞增殖、分化和凋亡，并介导上皮-间充质转化和细胞接触抑制。它已逐渐成为糖尿病肾病（DN）领域的热点。Tea 结构域（TEAD）是一种具有脱氧核糖核酸（DNA）结合域的因子，与激活的 YAP 结合，控制其重要靶因子-结缔组织生长因子（CTGF）的表达。
我们研究了 YAP 在 2 型糖尿病肾病中的作用，并评估了 YAP 与 2 型糖尿病肾病进展的相关性。我们通过免疫组化和免疫荧光染色检测了正常人和 51 例 DN 患者中 YAP、TEAD 和 CTGF 的表达，并评估了 2 型糖尿病肾病中临床、病理数据与 YAP 表达之间的关系。
在 2 型糖尿病肾病患者的肾脏中，YAP、TEAD 和 CTGF 在肾小球足细胞的核内高表达。然而，在这些健康肾脏中，上述三种因子主要表达在细胞质中。此外，DN 中 YAP 的高表达与收缩压（SBP）升高（r=0.484，p=0.019）、血尿素氮（BUN）升高（r=0.522，p=0.032）、肌酐（Cr）升高（r=0.496，p=0.031）、DN 分期进展（r=0.647，p=0.001）和 DN 病理分级进展（r=0.298，p=0.033）相关。此外，血清白蛋白（SAlb）降低（r=-0.656，p=0.001）和估算肾小球滤过率（eGFR）降低（r=-0.607，p=0.006）也与 DN 中 YAP 的高表达相关。
肾脏组织中 YAP、TEAD 和 CTGF 的高表达表明 YAP 在 2 型糖尿病肾病的肾损伤中发挥了重要作用。与 SBP、BUN、Cr、DN 分期、DN 病理分级、SAlb 和 eGFR 相关的 YAP 表明抑制 YAP 的活性可能具有延缓 DN 进展的作用。
