Low-dose of multi-glycoside of Tripterygium wilfordii Hook. f., a natural regulator of TGF-β1/Smad signaling activity improves adriamycin-induced glomerulosclerosis in vivo

SMAD公司 雷公藤 肾小球硬化 医学 足细胞 药理学 体内 转化生长因子 内科学 肾功能 雷公藤 信号转导 内分泌学 蛋白尿 化学 生物 细胞生物学 病理 糖苷 替代医学 生物技术 有机化学
作者
Yi‐Gang Wan,Xiao-Yan Che,Wei Sun,Yanru Huang,Xian‐Jie Meng,Hao-Li Chen,Xi-Miao Shi,Yue Tu,Wei Wu,Yinglu Liu
出处
期刊:Journal of Ethnopharmacology [Elsevier]
卷期号:151 (3): 1079-1089 被引量:38
标识
DOI:10.1016/j.jep.2013.12.005
摘要

Transforming growth factor (TGF)-β1/Smad signaling pathway plays a critical role in the prolonged glomerulosclerosis (GS), which is an important determinant during the progression in chronic kidney disease (CKD). For recent 30 years, multi-glycoside of Tripterygium wilfordii Hook. f. (GTW), an extract from Chinese herbal medicine has been proved clinically effective in improving GS in CKD in China. However, therapeutic mechanisms involved in vivo are still unclear. In this study, we aimed to explain the dose-effects and molecular mechanisms of GTW on GS by regulating TGF-β1/Smad signaling activity in adriamycin (ADR)-induced nephropathy (ADRN). Rats with ADRN, created by unilateral nephrectomy and twice adriamycin injections (ADR, 4 mg/kg and 2 mg/kg) within 4 weeks, were divided into four groups, the Sham group, the Vehicle group, the low-dose GTW-treated group, and the high-dose GTW-treated group, and that, sacrificed at the end of the 6th week after administration. Proteinuria, blood biochemical parameters, glomerulosclerotic morphological makers, podocyte shape, and nephrin expression were examined, respectively. Protein expressions of key signaling molecules in TGF-β1/Smad pathway, such as TGF-β1, Smad3, phosphorylated-Smad2/3 (p-Smad2/3), and Smad7, were also evaluated individually. The results indicated that the characterizations of ADRN involved the typical prolonged GS, a small amount of abnormal proteinuria, and the failing renal function; TGF-β1/Smad signaling molecules, especially Smad3, p-Smad2/3, and Smad7 were activated in vivo, accompanied by the exasperation of glomerulosclerotic lesion; GTW at high-dose (100 mg/kg) and low-dose (50 mg/kg) could slightly ameliorate the prolonged GS and nephrin expression, furthermore, the anti-proliferative action of GTW at high-dose was superior to that at low-dose, but caused the significant liver injury; in ADRN model rats, protein expressions of TGF-β1, p-Smad2/3, and Smad7 in the kidneys could be regulated with the treatment of GTW at low-dose. This study farther demonstrated that the low-dose of GTW, as a natural regulator in vivo, could effectively and safely ameliorate the prolonged GS in FSGS model, via the potential molecular mechanisms involving the reduction of ECM components and the suppression of TGF-β1 over-expression, as well as the bidirectional regulation of TGF-β1/Smad signaling activity.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
秋秋发布了新的文献求助20
1秒前
葡萄成熟应助Islet采纳,获得10
2秒前
科研通AI2S应助Josh采纳,获得10
4秒前
Ac发布了新的文献求助10
6秒前
LaiC完成签到,获得积分10
6秒前
欢喜寄云发布了新的文献求助10
6秒前
传奇3应助葡萄成熟采纳,获得10
7秒前
Wang完成签到,获得积分10
7秒前
顺利问玉完成签到,获得积分10
7秒前
evermore完成签到,获得积分10
7秒前
7秒前
杨春天完成签到,获得积分10
9秒前
11秒前
12秒前
6666发布了新的文献求助10
12秒前
evermore发布了新的文献求助10
13秒前
星辰大海应助xiyue采纳,获得10
13秒前
李li关注了科研通微信公众号
14秒前
michaelxia发布了新的文献求助10
17秒前
我的苞娜公主完成签到,获得积分10
17秒前
yxsccjj完成签到 ,获得积分10
18秒前
wen关闭了wen文献求助
18秒前
Endonucl关注了科研通微信公众号
19秒前
20秒前
11完成签到,获得积分10
23秒前
24秒前
6666完成签到,获得积分10
26秒前
26秒前
牡松发布了新的文献求助10
31秒前
32秒前
32秒前
科研通AI2S应助聪慧的南风采纳,获得10
35秒前
Wang关注了科研通微信公众号
36秒前
rachel发布了新的文献求助10
36秒前
璐璐发布了新的文献求助10
36秒前
36秒前
37秒前
39秒前
无花果应助悲凉的诺言采纳,获得10
39秒前
一一应助Cupid采纳,获得30
39秒前
高分求助中
The ACS Guide to Scholarly Communication 2500
Sustainability in Tides Chemistry 2000
Microlepidoptera Palaearctica, Volumes 1 and 3 - 13 (12-Volume Set) [German] 1122
The Data Economy: Tools and Applications 1000
Diamonds: Properties, Synthesis and Applications 800
PraxisRatgeber Mantiden., faszinierende Lauerjäger. – Buch gebraucht kaufen 700
Mantiden - Faszinierende Lauerjäger – Buch gebraucht kaufen 700
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3097793
求助须知:如何正确求助?哪些是违规求助? 2749704
关于积分的说明 7605682
捐赠科研通 2401576
什么是DOI,文献DOI怎么找? 1274203
科研通“疑难数据库(出版商)”最低求助积分说明 616015
版权声明 599016