Nio Yasunori, Okawara Mitsugi, Okuda Shoki, Matsuo Takanori, Furuyama Naoki
Extra Value Generation and General Medicine Drug Discovery Unit, Fujisawa, Kanagawa 251-8555, Japan.
Cardiovascular and Metabolic Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Fujisawa, Kanagawa 251-8555, Japan.
J Endocr Soc. 2017 May 16;1(7):772-786. doi: 10.1210/js.2017-00123. eCollection 2017 Jul 1.
Podocan, a member of the small leucine-rich repeat proteoglycans (SLRPs), is expressed in vascular endothelial cells with high levels of expression in the sclerotic glomerular lesions of experimental HIV-associated nephropathy. It is also found in vascular smooth muscle cells and is involved in atherosclerosis. Decorin, a protein similar to podocan, also belongs to the SLRP family and is highly expressed in adipose tissues. It is a secreted protein associated with obesity, type 2 diabetes, and diabetic nephropathy. Based on the similarity of podocan to decorin and its functions reported in the renal and cardiovascular systems, we hypothesized that podocan levels might correlate with the occurrence of metabolic syndromes such as obesity, diabetes, and diabetic nephropathy. We found that podocan was highly expressed in the adipose tissue of mice and humans and its expression was regulated by tumor necrosis factor- in mouse 3T3-L1 adipocytes. In addition, podocan was detected in the plasma, and its levels tended to increase in diet-induced obese C57BL/6J mice and decrease in obese-diabetic KKA and db/db mice. Podocan messenger RNA (mRNA) levels in the renal cortex correlated negatively with the urinary albumin-to-creatinine ratio, a surrogate marker of glomerular injury in uninephrectomized db/db mice used as a model of diabetic nephropathy. Our results suggest that podocan is involved in kidney function and could be a unique therapeutic target for diabetic nephropathy.
多配体蛋白聚糖（Podocan）是富含亮氨酸的小分子重复蛋白聚糖（SLRP）家族成员之一，在血管内皮细胞中表达，在实验性HIV相关性肾病的硬化性肾小球病变中表达水平较高。它也存在于血管平滑肌细胞中，并参与动脉粥样硬化。核心蛋白聚糖（Decorin）是一种与多配体蛋白聚糖相似的蛋白质，也属于SLRP家族，在脂肪组织中高度表达。它是一种与肥胖、2型糖尿病和糖尿病肾病相关的分泌蛋白。基于多配体蛋白聚糖与核心蛋白聚糖的相似性及其在肾脏和心血管系统中报道的功能，我们推测多配体蛋白聚糖水平可能与肥胖、糖尿病和糖尿病肾病等代谢综合征的发生有关。我们发现多配体蛋白聚糖在小鼠和人类的脂肪组织中高度表达，其表达在小鼠3T3-L1脂肪细胞中受肿瘤坏死因子调节。此外，在血浆中检测到多配体蛋白聚糖，在饮食诱导的肥胖C57BL/6J小鼠中其水平趋于升高，而在肥胖糖尿病KKA和db/db小鼠中其水平降低。在作为糖尿病肾病模型的单侧肾切除db/db小鼠中，肾皮质中的多配体蛋白聚糖信使核糖核酸（mRNA）水平与尿白蛋白与肌酐比值呈负相关，尿白蛋白与肌酐比值是肾小球损伤的替代标志物。我们的结果表明，多配体蛋白聚糖参与肾功能，可能是糖尿病肾病独特的治疗靶点。
