Pleckstrin同源域家族A成员1在代谢性疾病中的作用

doi:10.16352/j.issn.1001-6325.2025.02.0268

基础医学与临床 ›› 2025, Vol. 45 ›› Issue (2): 268-272.doi: 10.16352/j.issn.1001-6325.2025.02.0268

Pleckstrin同源域家族A成员1在代谢性疾病中的作用

胡艳敏¹, 彭丽娜², 杨勇², 向韵瑄¹, 常晓悦^1,2*

1.内蒙古医科大学包头临床医学院,包头 014040;
2.包头市中心医院呼吸与危重症医学科,包头 014040

收稿日期:2024-07-15 修回日期:2024-11-04 出版日期:2025-02-05 发布日期:2025-01-17
通讯作者: ^*btchangxiaoyue@163.com
基金资助:
包头市卫生健康科技计划项目(2024wsjkkj10)

The role of pleckstrin homology-like domain family A member 1 in metabolic diseases

HU Yanmin¹, PENG Lina², YANG Yong², XIANG Yunxuan¹, CHANG Xiaoyue^1,2*

1. Baotou Clinical Medical College, Inner Mongolia Medical University, Baotou 014040;
2. Department of Pulmonary and Critical Care Medicine, Baotou Central Hospital, Baotou 014040,China

Received:2024-07-15 Revised:2024-11-04 Online:2025-02-05 Published:2025-01-17
Contact: ^*btchangxiaoyue@163.com

摘要/Abstract

摘要： Pleckstrin同源域家族A成员1(PHLDA1)是一种促凋亡因子,也是代谢性疾病的关键调节剂。在肥胖相关疾病中,PHLDA1可以通过抑制固醇调控元素结合蛋白1(SREBP-1)的表达而减少肝三酰甘油的产生,也可通过抑制过氧化物酶体增殖剂激活受体γ(PPARγ)减少脂肪形成,但在心脑血管疾病中,却通过抑制PPARγ而增加血管钙化,刺激内质网应激反应(ERS)及线粒体功能障碍的产生,进而加重心脑缺血再灌注损伤。PHLDA1所表现出的双重作用也在肿瘤中得到印证。总之,PHLDA1作为多功能因子通过多种机制发挥不同作用。

关键词: pleckstrin同源域家族A成员1, 内质网应激反应, 肥胖, 心血管疾病

Abstract: Pleckstrin homology-like domain family A member 1 (PHLDA1) is a pro-apoptotic factor as well as a key regulator of metabolic diseases. In obesity-related diseases, PHLDA1 can reduce liver triglyceride production through inhibition of the expression of sterol regulatory-element binding proteins-1 (SREBP-1), and reduce fat synthesis through inhibition of peroxisome proliferator-activated receptor γ (PPARγ). However, in cardiovascular diseases, PHLDA1 increases vascular calcification, dysfunction, thereby aggravates ischemia-reperfusion injury in the heart and brain. The dual role of PHLDA1 has also been confirmed in tumors. In summary, PHLDA1, as a multifunctional factor, plays different functional roles through various mechanisms.

Key words: pleckstrin homology-like domain family A member 1 (PHLDA1), endoplasmic reticulum stress, obese, cardiovascular diseases

中图分类号:

胡艳敏, 彭丽娜, 杨勇, 向韵瑄, 常晓悦. Pleckstrin同源域家族A成员1在代谢性疾病中的作用[J]. 基础医学与临床, 2025, 45(2): 268-272.

HU Yanmin, PENG Lina, YANG Yong, XIANG Yunxuan, CHANG Xiaoyue. The role of pleckstrin homology-like domain family A member 1 in metabolic diseases[J]. Basic & Clinical Medicine, 2025, 45(2): 268-272.

参考文献 23

[1]	Wu YL, Lin ZJ, Li CC, et al. Epigenetic regulation in metabolic diseases: mechanisms and advances in clinical study[J]. Signal Transduct Target Ther, 2023,8:98. doi: 10.1038/s41392-023-01333-7.
[2]	Yousof T,Byun H J,Chen J, et al.Pleckstrin homology-like domain,family A,member 1(PHLDA1):a multifaceted cell survival factor that drives metabolic disease[J].Engineering,2023,20:9-18.
[3]	Peng H, Wang J, Song X, et al. PHLDA1 suppresses TLR4-triggered proinflammatory cytokine production by interaction with tollip[J].Front Immunol, 2022,13:731500. doi: 10.3389/fimmu.2022.731500.
[4]	Powis G, Meuillet EJ, Indarte M, et al. Pleckstrin homology[PH]domain, structure, mechanism, and contribution to human disease[J].Biomed Pharmacother, 2023,165:115024. doi: 10.1016/j.biopha.2023.115024.
[5]	Yousof TR, Bouchard CC, Alb M, et al. Restoration of the ER stress response protein TDAG51 in hepatocytes mitigates NAFLD in mice[J].J Biol Chem, 2024,300:105655. doi: 10.1016/j.jbc.2024.105655.
[6]	Kim S, Lee N, Park ES, et al.T-Cell death associated gene 51 is a novel negative regulator of PPARγ that inhibits PPARγ-RXRα heterodimer formation in adipogenesis[J].Mol Cells, 2021,44:1-12. doi: 10.14348/molcells.2020.0143.
[7]	Wong M, Forno E, Celedón JC. Asthma interactions between obesity and other risk factors[J].Ann Allergy Asthma Immunol, 2022,129:301-306.doi: 10.1016/j.anai.2022.04.029.
[8]	Bantulà M, Arismendi E, Tubita V, et al. Effect of obesity on the expression of genes associated with severe asthma-a pilot study[J]. J Clin Med, 2023,12:4398.doi: 10.3390/jcm12134398.
[9]	Chen Z, Zhang SL. Endoplasmic reticulum stress: a key regulator of cardiovascular disease[J]. DNA Cell Biol, 2023,42:322-335. doi: 10.1089/dna.2022.0532.
[10]	Platko K, Lebeau PF, Gyulay G, et al. TDAG51 (T-cell death-associated gene 51) is a key modulator of vascular calcification and osteogenic transdifferentiation of arterial smooth muscle cells[J]. Arterioscler Thromb Vasc Biol,2020,40:1664-1679. doi: 10.1161/atvbaha.119.313779.
[11]	Liu Y, Zhao H, Chen N, et al. PHLDA1 knockdown alleviates mitochondrial dysfunction and endoplasmic reticulum stress-induced neuronal apoptosis via activating PPARγ in cerebral ischemia-reperfusion injury[J]. Brain Res Bull,2023,194:23-34. doi: 10.1016/j.brainresbull.2023.01.007.
[12]	Guo Y, Jia P, Chen Y, et al. PHLDA1 is a new therapeutic target of oxidative stress and ischemia reperfusion-induced myocardial injury[J].Life Sci, 2020,245:117347. doi: 10.1016/j.lfs.2020.117347.
[13]	Carlisle RE, Mohammed-Ali Z, Lu C, et al. TDAG51 induces renal interstitial fibrosis through modulation of TGF-β receptor 1 in chronic kidney disease[J]. Cell Death Dis, 2021,12:921. doi: 10.1038/s41419-021-04197-3.
[14]	Wang X, Rao J, Chen X, et al. Identification of shared signature genes and immune microenvironment subtypes for heart failure and chronic kidney disease based on machine learning[J]. J Inflamm Res, 2024,17:1873-1895.doi: 10.2147/JIR.S450736. eCollection 2024.
[15]	Mk Nair P, Silwal K, Ramalakshmi R, et al.Beyond genetics: integrative oncology and the metabolic perspective on cancer treatment[J]. Front Oncol, 2024,14:1455022. doi: 10.3389/fonc.2024.1455022.
[16]	Xu J, Bi G, Luo Q, et al. PHLDA1 modulates the endoplasmic reticulum stress response and is required for resistance to oxidative stress-induced cell death in human ovarian cancer cells[J]. J Cancer,2021,12:5486-5493. doi: 10.7150/jca.45262.
[17]	Rahnama S, Tehrankhah ZM, Mohajerani F, et al. Milk thistle nano-micelle formulation promotes cell cycle arrest and apoptosis in hepatocellular carcinoma cells through modulating miR-155-3p /SOCS2 /PHLDA1 signaling axis[J]. BMC Complement Med Ther, 2023,23:337.doi: 10.1186/s12906-023-04168-5.
[18]	Yao B, Niu Y, Li Y, et al. High-matrix-stiffness induces promotion of hepatocellular carcinoma proliferation and suppression of apoptosis via miR-3682-3p-PHLDA1-FAS pathway[J]. J Cancer, 2020,11:6188-6203. doi: 10.7150/jca.45998.
[19]	Wang J, Yao N, Hu Y, et al. PHLDA1 promotes glioblastoma cell growth via sustaining the activation state of Ras[J]. Cell Mol Life Sci, 2022,79:520.doi: 10.1007/s00018-022-04538-1.
[20]	Iqbal S, Karim MR, Mohammad S, et al. Multiomics analysis of the PHLDA gene family in different cancers and their clinical prognostic value[J]. Curr Issues Mol Biol, 2024,46:5488-5510. doi: 10.3390/cimb46060328.
[21]	Huang R, Huang D, Wang S, et al. Repression of enhancer RNA PHLDA1 promotes tumorigenesis and progression of Ewing sarcoma via decreasing infiltrating T-lympho-cytes: a bioinformatic analysis[J]. Front Genet, 2022,13:952162.doi: 10.3389/fgene.2022.952162.
[22]	Duan Y, Du Y, Gu Z, et al. Prognostic value, immune signature, and molecular mechanisms of the PHLDA family in pancreatic adenocarcinoma[J]. Int J Mol Sci, 2022,23:10316. doi: 10.3390/ijms231810316.
[23]	Durbas M, Pabisz P, Wawak K, et al. GD2 ganglioside-binding antibody 14G2a and specific aurora A kinase inhibitor MK-5108 induce autophagy in IMR-32 neuroblastoma cells[J].Apoptosis,2018,23:492-511.doi: 10.1007/s10495-018-1472-9.

编辑推荐

Metrics

阅读次数

全文

HTML			PDF

最新录用	在线预览	正式出版	最新录用	在线预览	正式出版
0	0	0	0	0	6

	来源	本网站

	次数	6
	比例	100%

摘要

最新录用	在线预览	正式出版

0	0	45

Pleckstrin同源域家族A成员1在代谢性疾病中的作用

The role of pleckstrin homology-like domain family A member 1 in metabolic diseases

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献 23

相关文章 15

编辑推荐

Metrics

本文评价

[1]	杨剑锋, 郝琳, 王岩, 冀全博. 骨关节炎与心血管疾病交互影响的研究进展[J]. 基础医学与临床, 2025, 45(2): 148-153.
[2]	唐丽鸿, 陈春玲. SphK/S1P在心血管疾病中的作用[J]. 基础医学与临床, 2024, 44(8): 1175-1179.
[3]	加孜热亚·再依拿提, 李素丽, 张凯迪, 马福慧, 马国英, 郭艳英. 桥本甲状腺炎中辅助T细胞及其细胞因子与腹型肥胖相关[J]. 基础医学与临床, 2024, 44(8): 1120-1125.
[4]	丁宝锋, 王小爽, 王芳, 余佳. 肥胖模型小鼠肝脏的病理变化及代谢组分析[J]. 基础医学与临床, 2024, 44(5): 699-704.
[5]	张沥元, 杜函泽, 潘慧. 治疗下丘脑性肥胖的药物研究进展[J]. 基础医学与临床, 2024, 44(5): 729-732.
[6]	卢慧莹, 王建国. 下调去甲基化酶FTO抑制人肝癌细胞系HepG2增殖[J]. 基础医学与临床, 2024, 44(2): 185-191.
[7]	廖镇城, 杨思懿, 吴平安. 提高m⁶A去甲基化酶FTO表达抑制鼻咽癌细胞增殖[J]. 基础医学与临床, 2024, 44(1): 57-62.
[8]	马国英, 加孜热亚·再依拿提, 李素丽, 郭艳英. 基于血清蛋白质组学分析桥本甲状腺炎合并肥胖患者血清蛋白质差异表达[J]. 基础医学与临床, 2023, 43(9): 1375-1382.
[9]	陈辛, 陈俊, 徐幸, 王旭. 组蛋白去甲基化酶抑制剂GSK-J4减轻高脂诱导的肥胖小鼠体质量[J]. 基础医学与临床, 2023, 43(9): 1353-1358.
[10]	王鑫瑞, 秦燕. Ghrelin在代谢性疾病中作用的研究进展[J]. 基础医学与临床, 2023, 43(8): 1299-1303.
[11]	高源, 郑刚, 齐靖, 张凤. NLRP3炎性小体在心脏病发病中的作用研究进展[J]. 基础医学与临床, 2023, 43(7): 1162-1166.
[12]	张晶, 吴凯, 黄伟. 人前体脂肪细胞分化过程及肥胖人群脂肪组织中hsa_circ_0017650高表达[J]. 基础医学与临床, 2023, 43(7): 1079-1083.
[13]	蒋晨晨, 崔泽, 潘利, 孙纪新, 何慧婧, 胡耀达, 单广良. 河北省汉族和满族成人高血压家族史与超重/肥胖对高血压发病的交互作用[J]. 基础医学与临床, 2023, 43(7): 1053-1059.
[14]	杜丰禾, 刘暴. 血管周围脂肪组织炎性反应促进动脉粥样硬化作用机制的研究进展[J]. 基础医学与临床, 2023, 43(4): 685-689.
[15]	沈霞芬, 蔡强, 俞蔚, 许晓辉. 心血管疾病高危人群的影响因素及其关联分析[J]. 基础医学与临床, 2023, 43(11): 1655-1661.