Laboratory of Renal Physiology and Experimental Nephrology, Department of Biological Systems/Physiology Unit, University of Alcalá, Alcalá de Henares, Madrid, Spain.
J Diabetes Res. 2013;2013:162846. doi: 10.1155/2013/162846. Epub 2013 Jul 31.
Parathyroid hormone-related protein (PTHrP) and its receptor type 1 (PTH1R) are extensively expressed in the kidney, where they are able to modulate renal function. Renal PTHrP is known to be overexpressed in acute renal injury. Recently, we hypothesized that PTHrP involvement in the mechanisms of renal injury might not be limited to conditions with predominant damage of the renal tubulointerstitium and might be extended to glomerular diseases, such as diabetic nephropathy (DN). In experimental DN, the overexpression of both PTHrP and the PTH1R contributes to the development of renal hypertrophy as well as proteinuria. More recent data have shown, for the first time, that PTHrP is upregulated in the kidney from patients with DN. Collectively, animal and human studies have shown that PTHrP acts as an important mediator of diabetic renal cell hypertrophy by a mechanism which involves the modulation of cell cycle regulatory proteins and TGF- β 1. Furthermore, angiotensin II (Ang II), a critical factor in the progression of renal injury, appears to be responsible for PTHrP upregulation in these conditions. These findings provide novel insights into the well-known protective effects of Ang II antagonists in renal diseases, paving the way for new therapeutic approaches.
甲状旁腺激素相关蛋白 (PTHrP) 和其受体类型 1 (PTH1R) 在肾脏中广泛表达，能够调节肾脏功能。已知肾 PTHrP 在急性肾损伤中过度表达。最近，我们假设 PTHrP 参与肾损伤机制的作用可能不仅限于以肾小管间质损伤为主的情况，还可能扩展到肾小球疾病，如糖尿病肾病 (DN)。在实验性 DN 中，PTHrP 和 PTH1R 的过度表达均有助于肾肥大和蛋白尿的发生。最近的数据首次表明，DN 患者的肾脏中 PTHrP 上调。综上所述，动物和人体研究表明，PTHrP 通过调节细胞周期调节蛋白和 TGF-β1 作为糖尿病肾细胞肥大的重要介质。此外，血管紧张素 II (Ang II)，在肾损伤进展中的关键因素，似乎负责这些情况下 PTHrP 的上调。这些发现为 Ang II 拮抗剂在肾脏疾病中的众所周知的保护作用提供了新的见解，为新的治疗方法铺平了道路。
