Matsuki Kota, Hathaway Catherine K, Lawrence Marlon G, Smithies Oliver, Kakoki Masao
Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, CB #7525, 701 Brinkhous-Bullitt Building, Chapel Hill, NC 27599-7525, USA.
Curr Hypertens Rev. 2014;10(4):223-38. doi: 10.2174/157340211004150319123313.
Although human association studies suggest a link between polymorphisms in the gene encoding transforming growth factor (TGF) β1 and differing blood pressure levels, a causative mechanism for this correlation remains elusive. Recently we have generated a series of mice with graded expression of TGFβ1, ranging from approximately 10% to 300% compared to normal. We have found that blood pressure and plasma volume are negatively regulated by TGFβ1. Of note, the 10% hypomorph exhibits primary aldosteronism and markedly impaired urinary excretion of water and electrolytes. We here review previous literature highlighting the importance of TGFβ signaling as a natriuretic system, which we postulate is a causative mechanism explaining how polymorphisms in TGFβ1 could influence blood pressure levels.
尽管人类关联研究表明,编码转化生长因子(TGF)β1的基因多态性与不同的血压水平之间存在联系,但这种相关性的致病机制仍不清楚。最近,我们培育了一系列TGFβ1表达呈梯度变化的小鼠,与正常小鼠相比,其表达水平约为10%至300%。我们发现,TGFβ1对血压和血浆容量具有负向调节作用。值得注意的是,10%低表达型小鼠表现出原发性醛固酮增多症,水和电解质的尿排泄明显受损。我们在此回顾以往的文献,强调TGFβ信号作为一种利钠系统的重要性,我们推测这是一种致病机制,可解释TGFβ1基因多态性如何影响血压水平。