Transforming Growth Factorβ1 Overexpression Is Associated with Insulin Resistance and Rapidly Progressive Kidney Fibrosis under Diabetic Conditions.
Transforming Growth Factorβ1 Overexpression Is Associated with Insulin Resistance and Rapidly Progressive Kidney Fibrosis under Diabetic Conditions.
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DOI：
10.3390/ijms232214265
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发表时间：
2022-11-17
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
糖尿病是一个全球性的健康问题。糖尿病肾病是糖尿病的常见并发症，是导致终末期肾病的主要原因。糖尿病肾病患者的临床病程、治疗反应和预后均比非糖尿病患者差。转化生长因子β1在肾纤维化中的作用尚不明确。本研究评估了转化生长因子β1的过度表达是否与胰岛素抵抗和糖尿病条件下转化生长因子β1介导的肾病快速进展相关。在野生型小鼠和肾脏特异性过表达人转化生长因子β1的转基因小鼠中，用链脲佐菌素诱导糖尿病。用盐水处理的小鼠为对照。评估葡萄糖耐量和肾纤维化。与非糖尿病转基因小鼠、糖尿病野生型小鼠和非糖尿病小鼠相比，糖尿病转化生长因子β1转基因小鼠的血糖水平、胰岛素抵抗稳态模型评估值和肾纤维化面积显著增加，肾功能显著受损。在肝细胞和骨骼肌细胞系中，转化生长因子β1可削弱胰岛素对葡萄糖的调节作用。这项研究表明，转化生长因子β1过表达与胰岛素抵抗和糖尿病条件下小鼠快速进行性肾纤维化有关。
Diabetes mellitus is a global health problem. Diabetic nephropathy is a common complication of diabetes mellitus and the leading cause of end-stage renal disease. The clinical course, response to therapy, and prognosis of nephropathy are worse in diabetic than in non-diabetic patients. The role of transforming growth factorβ1 in kidney fibrosis is undebatable. This study assessed whether the overexpression of transforming growth factorβ1 is associated with insulin resistance and the rapid progression of transforming growth factorβ1-mediated nephropathy under diabetic conditions. Diabetes mellitus was induced with streptozotocin in wild-type mice and transgenic mice with the kidney-specific overexpression of human transforming growth factorβ1. Mice treated with saline were the controls. Glucose tolerance and kidney fibrosis were evaluated. The blood glucose levels, the values of the homeostasis model assessment for insulin resistance, and the area of kidney fibrosis were significantly increased, and the renal function was significantly impaired in the diabetic transforming growth factorβ1 transgenic mice compared to the non-diabetic transgenic mice, diabetic wild-type mice, and non-diabetic mice. Transforming growth factorβ1 impaired the regulatory effect of insulin on glucose in the hepatocyte and skeletal muscle cell lines. This study shows that transforming growth factorβ1 overexpression is associated with insulin resistance and rapidly progressive kidney fibrosis under diabetic conditions in mice.
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影响因子：
5.6
作者：
Hung PH;Hsu YC;Chen TH;Lin CL
通讯作者：
Lin CL
影响因子：
7.7
作者：
Alessi, MC;Bastelica, D;Juhan-Vague, I
通讯作者：
Juhan-Vague, I
影响因子：
19.6
作者：
Hoffman, BB;Sharma, K;Ziyadeh, FN
通讯作者：
Ziyadeh, FN
影响因子：
2.3
作者：
Bellasi A;Di Micco L;Santoro D;Marzocco S;De Simone E;Cozzolino M;Di Lullo L;Guastaferro P;Di Iorio B;UBI study investigators
通讯作者：
UBI study investigators
影响因子：
7.7
作者：
Dantas, Wagner S.;Roschel, Hamilton;Gualano, Bruno
通讯作者：
Gualano, Bruno