GPX4介导铁死亡在TGF-β/Smad3依赖的肾脏纤维化的作用和机制研究

批准号:
81970641
项目类别:
面上项目
资助金额:
53.0 万元
负责人:
钟翔
依托单位:
学科分类:
慢性肾脏病及其并发症
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
钟翔
国基评审专家1V1指导 中标率高出同行96.8%
结合最新热点,提供专业选题建议
深度指导申报书撰写,确保创新可行
指导项目中标800+,快速提高中标率
微信扫码咨询
中文摘要
肾纤维化是各种慢性肾脏病进展及预后的重要指标。TGF-β/Smad3依赖的信号通路对肾纤维化有重要作用。铁死亡是GPX4介导、铁参与的氧化损伤。前期研究在IgA肾病、糖尿病肾病、TGF-β1刺激的大鼠肾小管上皮细胞(rTEC)及单侧输尿管梗阻(UUO)小鼠肾纤维化中,TGF-β/Smad3激活伴铁死亡增加;体外诱导或抑制铁死亡表达增强或减轻TGF-β1诱导的rTEC纤维化;SIS3特异性抑制Smad3的rTEC及Smad3基因敲除UUO小鼠GPX4上升;TGF-β1刺激24h后,confocal及CO-IP提示P-Smad3与GPX4共表达并相互作用,由此推测:TGF-β/Smad3通过GPX4介导铁死亡作用于肾脏纤维化。我们将进一步证实GPX4介导铁死亡参与TGF-β/Smad3依赖肾纤维化,并多方面干预铁死亡深入研究其在肾纤维化的作用及具体机制。课题将为肾纤维化机制和治疗提供新的方向。
英文摘要
Renal fibrosis is an important indicator for the progression and prognosis of all CKD patients. TGF-beta/Smad3-dependent signaling pathway plays an important role in renal fibrosis. Ferroptosis is GPX4-mediated and driven by iron-dependent lipid peroxidation. Previous studies showed that in IgA nephropathy, diabetic nephropathy, TGF-beta-1-stimulated rat tubular epithelial cell (rTEC) and unilateral ureteral obstruction (UUO) mice, activation of TGF-beta/Smad3 accompanied with increased ferroptosis; induction or inhibition of ferroptosis expression enhanced or alleviated TGF-beta-1-induced renal fibrosis; In SIS3 specifically inhibited Smad3 rTEC and Smad3 conditional knock out UUO mice, the GPX4 expression was observed significantly up-regulated ; confocal and CO-IP results suggested that the P-Smad3 and GPX4 was co-expressed in rTEC and physically combined with each other after TGF-beta-1 stimulated for 24 hours. Therefore, we hypothesize that TGF-beta/Smad3 acts on renal fibrosis through GPX4-mediated ferroptosis. We will further directly confirm that ferroptosis is involved in TGF-beta/Smad3-dependent renal fibrosis. We also will use ferroptosis-specific inducers or inhibitors and GPX4 inhibitors to intervene the expression of ferroptosis and observe its effect on renal fibrosis, and further explore the mechanism of ferroptosis on renal fibrosis. This study will provide a new direction for the mechanism and treatment of renal fibrosis.
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
DOI:10.1186/s12920-021-00969-0
发表时间:2021-05-08
期刊:BMC medical genomics
影响因子:2.7
作者:Fan S;Wang Q;Wang AY;Zhang P;Zhong X;Chen S;Li G;Wang L;Wang W
通讯作者:Wang W
DOI:10.1080/0886022x.2022.2114370
发表时间:2022-12
期刊:Renal failure
影响因子:3
作者:
通讯作者:
DOI:10.21037/apm-21-2065
发表时间:2021-09
期刊:Annals of palliative medicine
影响因子:--
作者:Xueyu Zhan;Fei Deng;A. Wang;Qin Chen;Yongjing Du;Qiuxia Wang;X. Zhong;Ping Zhang;Wen Wang;Shasha Chen;Guisen Li;Li Wang
通讯作者:Xueyu Zhan;Fei Deng;A. Wang;Qin Chen;Yongjing Du;Qiuxia Wang;X. Zhong;Ping Zhang;Wen Wang;Shasha Chen;Guisen Li;Li Wang
DOI:10.3390/jcm12185789
发表时间:2023-09-06
期刊:Journal of clinical medicine
影响因子:3.9
作者:
通讯作者:
Ubiquitin-specific protease 47 is associated with vascular calcification in chronic kidney disease by regulating osteogenic transdifferentiation of vascular smooth muscle cells.
泛素特异性蛋白酶47通过调节血管平滑肌细胞的成骨转分化,与慢性肾脏疾病中的血管钙化有关。
DOI:10.1080/0886022x.2022.2072337
发表时间:2022-12
期刊:Renal failure
影响因子:3
作者:
通讯作者:
WISP-1在肾脏纤维化中的功能定位及其机制研究
- 批准号:81300618
- 项目类别:青年科学基金项目
- 资助金额:23.0万元
- 批准年份:2013
- 负责人:钟翔
- 依托单位:
国内基金
海外基金
