上海交通大学学报（医学版）

上海交通大学学报（医学版） >

2025 , Vol. 45 >Issue 7: 910 - 915

DOI: https://doi.org/10.3969/j.issn.1674-8115.2025.07.013

综述

精氨酸代谢调控间充质干细胞功能的研究进展

  • 赛提尔古丽·克然木 ,
  • 钱蕾 ,
  • 丁思怡 ,
  • 哈娜提·马合力木汗 ,
  • 杨雪儿 ,
  • 贾浩
展开
  • 上海交通大学基础医学院生物化学与分子细胞生物学系，上海市肿瘤微环境与炎症重点实验室，上海 200025
贾　浩，研究员，博士；电子信箱：fonney@sjtu.edu.cn。

收稿日期: 2024-11-20

  录用日期: 2025-04-15

  网络出版日期: 2025-07-16

基金资助

国家自然科学基金(31970679);上海市自然科学基金(24ZR1441300)

收起

Research progress of arginine metabolism in the regulation of mesenchymal stem cell function

  • KERANMU Saitierguli ,
  • QIAN Lei ,
  • DING Siyi ,
  • MAHELIMUHAN Hanati ,
  • YANG Xueer ,
  • JIA Hao
Expand
  • Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University College of Basic Medical Sciences, Shanghai 200025, China
JIA Hao, E-mail: fonney@sjtu.edu.cn.

Received date: 2024-11-20

  Accepted date: 2025-04-15

  Online published: 2025-07-16

Supported by

National Natural Science Foundation of China(31970679);Natural Science Foundation of Shanghai(24ZR1441300)

Fold

摘要

间充质干细胞（mesenchymal stem cells，MSCs）是一类存在于骨髓、脂肪、脐带血、骨骼、肌肉等多种组织中的成体干细胞，不仅具有干细胞特有的自我更新能力和多向分化潜能，还具有免疫调节功能。精氨酸是一种条件必需氨基酸，其代谢调控对维持细胞功能和机体健康至关重要。精氨酸代谢可能对MSCs的增殖和分化、炎症反应的发生，以及肿瘤发展均有一定影响。该文总结精氨酸代谢对不同种类MSCs分化的作用及其与炎症、免疫、肿瘤发展之间的关系，探讨代谢综合征治疗的新策略，从精氨酸代谢角度为MSCs治疗炎症性疾病、肿瘤等提供新思路。

关键词： 间充质干细胞; 精氨酸代谢; 分化; 炎症

本文引用格式

赛提尔古丽·克然木 , 钱蕾 , 丁思怡 , 哈娜提·马合力木汗 , 杨雪儿 , 贾浩 . 精氨酸代谢调控间充质干细胞功能的研究进展[J]. 上海交通大学学报（医学版）, 2025 , 45(7) : 910 -915 . DOI: 10.3969/j.issn.1674-8115.2025.07.013

Abstract

Mesenchymal stem cells (MSCs) are adult stem cells that exist in bone marrow, fat, cord blood, bone, muscle and other tissues. MSCs not only have the unique self-renewal ability and multidirectional differentiation potential of stem cells, but also have the function of immune regulation. Arginine is a conditionally essential amino acid, and its metabolic regulation is essential for maintaining cell function and overall health. In MSCs, arginine metabolism may have a certain effect on cell proliferation, differentiation, inflammatory response, and tumor development. This article summarizes the effects of arginine metabolism on the differentiation, inflammation, immunity, and tumor development in different types of MSCs, discusses new strategies for the treatment of metabolic syndrome, and provides new ideas for the treatment of inflammatory diseases and tumors by MSCs from the perspective of arginine metabolism.

Key words： mesenchymal stem cells; arginine metabolism; cell differentiation; inflammation

参考文献

[1] HUH J E, CHOI J Y, SHIN Y O, et al. Arginine enhances osteoblastogenesis and inhibits adipogenesis through the regulation of Wnt and NFATc signaling in human mesenchymal stem cells[J]. Int J Mol Sci, 2014, 15(7): 13010-13029.
[2] YANG S, GUO L, SU Y, et al. Nitric oxide balances osteoblast and adipocyte lineage differentiation via the JNK/MAPK signaling pathway in periodontal ligament stem cells[J]. Stem Cell Res Ther, 2018, 9(1): 118.
[3] YI X, LIU J, WU P, et al. The whole transcriptional profiling of cellular metabolism during adipogenesis from hMSCs[J]. J Cell Physiol, 2020, 235(1): 349-363.
[4] NATARAJAN S K, ZHU W D, LIANG X W, et al. Proline dehydrogenase is essential for proline protection against hydrogen peroxide-induced cell death[J]. Free Radic Biol Med, 2012, 53(5): 1181-1191.
[5] ZHANG C, ZHEN Y, WENG Y, et al. Research progress on the microbial metabolism and transport of polyamines and their roles in animal gut homeostasis[J]. J Anim Sci Biotechnol, 2025, 16(1): 57.
[6] HASS R, KASPER C, B?HM S, et al. Different populations and sources of human mesenchymal stem cells (MSC): a comparison of adult and neonatal tissue-derived MSC[J]. Cell Commun Signal, 2011, 9: 12.
[7] 丁涵青, 张颖, 韦璐瑶, 等.精氨酸及其代谢产物对缺血性脑卒中的作用[J].现代生物医学进展, 2021, 21(11): 2179-2183.
  DING H Q, ZHANG Y, WEI L Y, et al. The role of arginine and its metabolites in ischemic stroke[J]. Progress in Modern Biomedicine, 2021, 21(11): 2179-2183.
[8] ZOU Z Q, CHENG Q, ZHOU J J, et al. ATF4-SLC7A11-GSH axis mediates the acquisition of immunosuppressive properties by activated CD4+ T cells in low arginine condition[J]. Cell Rep, 2024, 43(4): 113995.
[9] MOSSMANN D, MüLLER C, PARK S, et al. Arginine reprograms metabolism in liver cancer via RBM39[J]. Cell, 2023, 186(23): 5068-5083.e23.
[10] FENG S, RAO Z, ZHANG J, et al. Inhibition of CARM1-mediated methylation of ACSL4 promotes ferroptosis in colorectal cancer[J]. Adv Sci (Weinh), 2023, 10(36): e2303484.
[11] YOU S, LI S, ZENG L, et al. Lymphatic-localized Treg-mregDC crosstalk limits antigen trafficking and restrains anti-tumor immunity[J]. Cancer Cell, 2024, 42(8): 1415-1433.e12.
[12] CZERWIEC K, ZAWRZYKRAJ M, DEPTU?A M, et al. Adipose-derived mesenchymal stromal cells in basic research and clinical applications[J]. Int J Mol Sci, 2023, 24(4): 3888.
[13] SI Z Z, WANG X, SUN C H, et al. Adipose-derived stem cells: sources, potency, and implications for regenerative therapies[J]. Biomed Pharmacother, 2019, 114: 108765.
[14] OKUBO T, FUJIMOTO S, HAYASHI D, et al. Valproic acid promotes mature neuronal differentiation of adipose tissue-derived stem cells through iNOS-NO-sGC signaling pathway[J]. Nitric Oxide, 2019, 93: 1-5.
[15] HAYASHI D, OKUBO T, SUZUKI T, et al. Valproic acid up-regulates the whole NO-citrulline cycle for potent iNOS-NO signaling to promote neuronal differentiation of adipose tissue-derived stem cells[J]. Nitric Oxide, 2021, 106: 35-44.
[16] OKUBO T, HAYASHI D, YAGUCHI T, et al. Differentiation of rat adipose tissue-derived stem cells into neuron-like cells by valproic acid, a histone deacetylase inhibitor[J]. Exp Anim, 2016, 65(1): 45-51.
[17] KANG E S, KIM D S, HAN Y, et al. Three-dimensional graphene-RGD peptide nanoisland composites that enhance the osteogenesis of human adipose-derived mesenchymal stem cells[J]. Int J Mol Sci, 2018, 19(3): E669.
[18] MIRSAIDI A, GENELIN K, VETSCH J R, et al. Therapeutic potential of adipose-derived stromal cells in age-related osteoporosis[J]. Biomaterials, 2014, 35(26): 7326-7335.
[19] CAO S, LI Y X, SONG R, et al. L-arginine metabolism inhibits arthritis and inflammatory bone loss[J]. Ann Rheum Dis, 2024, 83(1): 72-87.
[20] PAN Q L, WANG D, CHEN D Y, et al. Characterizing the effects of hypoxia on the metabolic profiles of mesenchymal stromal cells derived from three tissue sources using chemical isotope labeling liquid chromatography-mass spectrometry[J]. Cell Tissue Res, 2020, 380(1): 79-91.
[21] CRUMP N T, HADJINICOLAOU A V, XIA M, et al. Chromatin accessibility governs the differential response of cancer and T cells to arginine starvation[J]. Cell Rep, 2021, 35(6): 109101.
[22] KUO M T, CHEN H H W, FEUN L G, et al. Targeting the proline-glutamine-asparagine-arginine metabolic axis in amino acid starvation cancer therapy[J]. Pharmaceuticals (Basel), 2021, 14(1): 72.
[23] MAZUREK M, ROLA R. The implications of nitric oxide metabolism in the treatment of glial tumors[J]. Neurochem Int, 2021, 150: 105172.
[24] KHAN F H, DERVAN E, BHATTACHARYYA D D, et al. The role of nitric oxide in cancer: master regulator or NOt?[J]. Int J Mol Sci, 2020, 21(24): E9393.
[25] ZHANG M S, JIN H, LIU Y, et al. L-Arginine self-delivery supramolecular nanodrug for NO gas therapy[J]. Acta Biomater, 2023, 169: 517-529.
[26] HUANG G T, GRONTHOS S, SHI S. Mesenchymal stem cells derived from dental tissues vs. those from other sources: their biology and role in regenerative medicine[J]. J Dent Res, 2009, 88(9): 792-806.
[27] SALIMIAN RIZI B, CANEBA C, NOWICKA A, et al. Nitric oxide mediates metabolic coupling of omentum-derived adipose stroma to ovarian and endometrial cancer cells[J]. Cancer Res, 2015, 75(2): 456-471.
[28] LAINO G, D′AQUINO R, GRAZIANO A, et al. A new population of human adult dental pulp stem cells: a useful source of living autologous fibrous bone tissue (LAB)[J]. J Bone Miner Res, 2005, 20(8): 1394-1402.
[29] MANASPON C, JONGWANNASIRI C, CHUMPRASERT S, et al. Human dental pulp stem cell responses to different dental pulp capping materials[J]. BMC Oral Health, 2021, 21(1): 209.
[30] STEENS J, KLAR L, HANSEL C, et al. The vascular nature of lung-resident mesenchymal stem cells[J]. Stem Cells Transl Med, 2021, 10(1): 128-143.
[31] MAJOLO F, DA SILVA G L, VIEIRA L, et al. Review of trials currently testing stem cells for treatment of respiratory diseases: facts known to date and possible applications to COVID-19[J]. Stem Cell Rev Rep, 2021, 17(1): 44-55.
[32] EBRAHIMI F, PIROUZMAND F, COSME PECHO R D, et al. Application of mesenchymal stem cells in regenerative medicine: a new approach in modern medical science[J]. Biotechnol Prog, 2023, 39(6): e3374.
[33] LU L L, LIU Y J, YANG S G, et al. Isolation and characterization of human umbilical cord mesenchymal stem cells with hematopoiesis-supportive function and other potentials[J]. Haematologica, 2006, 91(8): 1017-1026.
[34] HARRIS V K, STARK J, WILLIAMS A, et al. Efficacy of intrathecal mesenchymal stem cell-neural progenitor therapy in progressive MS: results from a phase Ⅱ, randomized, placebo-controlled clinical trial[J]. Stem Cell Res Ther, 2024, 15(1): 151.
[35] LIU Y Y, LI Y, WANG L, et al. Mesenchymal stem cell-derived exosomes regulate microglia phenotypes: a promising treatment for acute central nervous system injury[J]. Neural Regen Res, 2023, 18(8): 1657-1665.
[36] YU Z, ZHANG W, WANG Y, et al. Extracellular vesicles derived from human umbilical cord MSC improve vascular endothelial function in in vitro and in vivo models of preeclampsia through activating arginine metabolism[J]. Mol Pharm, 2023, 20(12): 6429-6440.
[37] HUANG Y C, YANG Z M, CHEN X H, et al. Isolation of mesenchymal stem cells from human placental decidua basalis and resistance to hypoxia and serum deprivation[J]. Stem Cell Rev Rep, 2009, 5(3): 247-255.
[38] BARLOW S, BROOKE G, CHATTERJEE K, et al. Comparison of human placenta- and bone marrow-derived multipotent mesenchymal stem cells[J]. Stem Cells Dev, 2008, 17(6): 1095-1107.
[39] CAHYADI A, UGRASENA I D G, ANDARSINI M R, et al. Relationship between Bax and Bcl-2 protein expression and outcome of induction phase chemotherapy in pediatric acute lymphoblastic leukemia[J]. Asian Pac J Cancer Prev, 2022, 23(5): 1679-1685.
[40] SHEN S F, HUA C H. Effect of L-arginine on the expression of Bcl-2 and Bax in the placenta of fetal growth restriction[J]. J Matern Fetal Neonatal Med, 2011, 24(6): 822-826.
[41] GAO Z, XUE M, WANG Z. LC-MS/MS assay to confirm that the endogenous metabolite L-arginine promotes trophoblast invasion in the placenta accreta spectrum through upregulation of the GPRC6A/PI3K/AKT pathway[J]. BMC Pregnancy Childbirth, 2025, 25(1): 402.
Options
文章导航

/

〈 〉