Role of coagulation factor 3 in diabetic nephropathy

糖尿病肾病是导致终末期肾病的主要原因，糖尿病肾病患者的数量正在迅速增加。人类内皮型一氧化氮合酶基因(eNOS，NOS3)产生的一氧化氮(NO)减少与糖尿病肾病呈正相关，尽管缺乏病因的证据。在这里，我们已经证明了eNOS-/-糖尿病小鼠会发展成严重的肾病。然而，尽管eNOS水平降低的情况并不少见，但在人类中还没有报道完全缺乏eNOS。因此，eNOS+/-杂合子小鼠已形成糖尿病，并且他们证明eNOS/NO的减少与NOS3基因的多态相当，足以导致糖尿病肾病的恶化。作为凝血的起始者，组织因子的表达增加在eNOS-/-糖尿病小鼠的糖尿病肾病中可能起着重要的作用。改善高凝状态的策略可能对糖尿病肾病的治疗有用。

Diabetic nephropathy (DN)is the leading cause of end stage renal disease, and the number of patients with DN has been increasing rapidly. Human variants of the endothelial nitric oxide synthase gene (eNOS, NOS3)that produce reduced amounts of nitric oxide (NO)are positively associated with DN, although proof of causation is lacking. Here we have demonstrated that eNOS-/-mice with diabetes develop severe nephropathy. However, complete absence of eNOS has not been reported in humans, although reduced levels are not infrequent. Accordingly, heterozygous eNOS+/-mice have been made diabetic, and they demonstrated that the decrease in eNOS/NO comparable to that of NOS3 polymorphisms is sufficient to cause exacerbation of DN. Increased expression of tissue factor, initiator of coagulation, likely plays a significant role in the DN of the eNOS-/-diabetic mice. Strategies to ameliorate hypercoagulability could be useful for treatment of DN.