HIF-1α promotes kidney organoid vascularization and applications in disease modeling

类有机物 诱导多能干细胞 干细胞 生物 血管生成 缺氧诱导因子 细胞生物学 祖细胞 癌症研究 内分泌学 胚胎干细胞 生物化学 基因
作者
Kexin Peng,Wei Xie,Tingting Wang,Yamei Li,Jean de Dieu Habimana,Obed Boadi Amissah,Jufang Huang,Yong Chen,Bin Ni,Zhiyuan Li
出处
期刊:Stem Cell Research & Therapy [BioMed Central]
卷期号:14 (1)
标识
DOI:10.1186/s13287-023-03528-9
摘要

Abstract Background Kidney organoids derived from human pluripotent stem cells (HiPSCs) hold huge applications for drug screening, disease modeling, and cell transplanting therapy. However, these applications are limited since kidney organoid cannot maintain complete morphology and function like human kidney. Kidney organoids are not well differentiated since the core of the organoid lacked oxygen, nutrition, and vasculature, which creates essential niches. Hypoxia-inducible factor-1 α (HIF-1α) serves as a critical regulator in vascularization and cell survival under hypoxia environment. Less is known about the role of HIF-1α in kidney organoids in this regard. This study tried to investigate the effect of HIF-1α in kidney organoid vascularization and related disease modeling. Methods For the vascularization study, kidney organoids were generated from human induced pluripotent stem cells. We overexpressed HIF-1α via plasmid transfection or treated DMOG (Dimethyloxallyl Glycine, an agent for HIF-1α stabilization and accumulation) in kidney progenitor cells to detect the endothelium. For the disease modeling study, we treated kidney organoid with cisplatin under hypoxia environment, with additional HIF-1α transfection. Result HIF-1α overexpression elicited kidney organoid vascularization. The endothelial cells and angiotool analysis parameters were increased in HIF-1α plasmid-transfected and DMOG-treated organoids. These angiogenesis processes were partially blocked by VEGFR inhibitors, semaxanib or axitinib. Cisplatin-induced kidney injury (Cleaved caspase 3) was protected by HIF-1α through the upregulation of CD31 and SOD2. Conclusion We demonstrated that HIF-1α elicited the process of kidney organoid vascularization and protected against cisplatin-induced kidney organoid injury in hypoxia environment.

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

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
刚刚
阳光沛柔发布了新的文献求助10
刚刚
YYYZZX1完成签到,获得积分10
1秒前
英俊的铭应助Ljc采纳,获得10
1秒前
Rondab应助杜兰特工队采纳,获得30
2秒前
2秒前
2秒前
2秒前
隐形曼青应助yuanyuan采纳,获得10
2秒前
3秒前
nini发布了新的文献求助10
4秒前
思源应助zxunxia采纳,获得10
6秒前
6秒前
6秒前
6秒前
7秒前
量子星尘发布了新的文献求助30
7秒前
XYN1发布了新的文献求助10
7秒前
直立行走完成签到,获得积分10
7秒前
nini完成签到,获得积分10
9秒前
yuanyuan完成签到,获得积分20
10秒前
11秒前
11秒前
我晕豆芽发布了新的文献求助10
12秒前
13秒前
14秒前
沐风发布了新的文献求助10
14秒前
hh发布了新的文献求助10
15秒前
15秒前
Ljc完成签到,获得积分10
16秒前
昏睡的绿海完成签到,获得积分10
17秒前
18秒前
润泽发布了新的文献求助10
18秒前
19秒前
寻悦发布了新的文献求助10
21秒前
冷静的羿发布了新的文献求助10
21秒前
22秒前
22秒前
Ljc发布了新的文献求助10
23秒前
星辰大海应助butter采纳,获得10
23秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 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 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3988920
求助须知:如何正确求助?哪些是违规求助? 3531290
关于积分的说明 11253247
捐赠科研通 3269903
什么是DOI,文献DOI怎么找? 1804830
邀请新用户注册赠送积分活动 882027
科研通“疑难数据库(出版商)”最低求助积分说明 809052