The Journal of Practical Medicine >

2024 , Vol. 40 >Issue 17: 2369 - 2374

DOI: https://doi.org/10.3969/j.issn.1006-5725.2024.17.003

Basic Research

Molecular mechanism of young Sca⁃1 bone marrow stem cell on old cardiac fibroblast cell apoptosis in aging mice

  • Rao Lü ,
  • Jiadi YU ,
  • Liuzhen LI ,
  • Chulan ZHAN ,
  • Liyue ZHAO ,
  • Yueliang LI ,
  • Jun DONG ,
  • Jiao. LI
Expand
  • *.Department of Cardiology，The Sixth School of Clinical Medicine，the Affiliated Qingyuan Hospital（Qingyuan People′s Hospital），Guangzhou Medical University，Qingyuan 511518，China
    *.Department of Geriatric，the Second Affiliated Hospital of Guangzhou Medical University，Guangzhou 510260，China

Received date: 2024-10-07

  Online published: 2024-09-13

Fold

Abstract

Objective To investigate the impact of Sca-1 bone marrow derived stem cells on apoptosis in murine cardiac fibroblasts and the molecular mechanisms of young （Y） Sca?1 bone marrow stem cell （BMSC） on old （O） cardiac fibroblast cell （CFC） apoptosis. Methods The apoptosis and survival of Y and O CFC were assessed under hypoxic conditions. Co-cultures of Y and O Sca-1 bone marrow-derived mesenchymal stem cells （BMSC） with O CFC were established to investigate the impact of Sca-1 BMSC on the apoptotic response and viability of O CFC， employing TUNEL staining， qRT-PCR， Western Blot， and CCK8 assays. Furthermore， differential secretion profiles of growth factors by Y and O Sca-1 BMSC were compared using qRT-PCR and ELISA analysis. Results Compared to Y CFC， O CFC exhibited an increased rate of apoptosis and a decreased rate of cell survival. However， when compared to O cells， Y Sca-1 BMC significantly reduced apoptosis in O CFC and enhanced cell survival. Moreover， Y Sca-1 BMSC demonstrated a higher secretion of GDF5 （Growth Differentiation Factor 5） than O cells （P < 0.05）. Importantly， the protective effects of Y Sca-1 BMSC on apoptosis and survival in O CFC were abolished upon neutralization of GDF5 expression. Conclusion Y Sca-1 BMSC decreases O CFC apoptosis through GDF5.

Key words： stem cell; cardiac fibroblast cell; apoptosis; cell survival; growth factors; Sca-1

Cite this article

Rao Lü , Jiadi YU , Liuzhen LI , Chulan ZHAN , Liyue ZHAO , Yueliang LI , Jun DONG , Jiao. LI . Molecular mechanism of young Sca⁃1 bone marrow stem cell on old cardiac fibroblast cell apoptosis in aging mice[J]. The Journal of Practical Medicine, 2024 , 40(17) : 2369 -2374 . DOI: 10.3969/j.issn.1006-5725.2024.17.003

References

1 RIBEIRO A S F， ZEROLO B E， LóPEZ-ESPUELA F， et al. Cardiac System during the Aging Process［J］. Aging Dis， 2023， 14（4）： 1105-1122.
2 XIE S， XU S C， DENG W， et al. Metabolic landscape in cardiac aging： insights into molecular biology and therapeutic implications［J］. Signal Transduct Target Ther， 2023， 8（1）： 114. doi:10.1038/s41392-023-01378-8
3 LAZZERONI D， VILLATORE A， SOURYAL G， et al. The Aging Heart： A Molecular and Clinical Challenge［J］. Int J Mol Sci， 2022，23（24）：16033. doi:10.3390/ijms232416033
4 李若男，杨俊，张静，等. 线粒体质量控制系统在心脏衰老中的研究进展［J］. 实用医学杂志， 2023，39（8）：1052-1057. doi:10.3969/j.issn.1006-5725.2023.08.023
5 MARVASTI T B， ALIBHAI F J， WLODAREK L， et al. Aging impairs human bone marrow function and cardiac repair following myocardial infarction in a humanized chimeric mouse［J］. Aging Cell， 2021， 20（11）： e13494. doi:10.1111/acel.13494
6 陈霞，武馨馨，刘星佑，等. 过表达NKx2.5基因间充质干细胞增强SDF-1/CXCR4轴促归巢改善心梗心功能［J］. 实用医学杂志， 2023，39（6）：660-666.
7 LI J， LI S H， DONG J， et al. Long-term repopulation of aged bone marrow stem cells using young Sca-1 cells promotes aged heart rejuvenation［J］. Aging Cell， 2019， 18（6）： e13026. doi:10.1111/acel.13026
8 MARUNOUCHI T， SASAKI K， YANO E， et al. Transplantation of cardiac Sca-1-positive cells rather than c-Kit-positive cells preserves mitochondrial oxygen consumption of the viable myocardium following myocardial infarction in rats［J］. J Pharmacol Sci， 2019， 140（3）： 236-241. doi:10.1016/j.jphs.2019.07.005
9 DASEKE M J 2 ND， TENKORANG M A A， CHALISE U，et al. Cardiac fibroblast activation during myocardial infarction wound healing： Fibroblast polarization after MI［J］. Matrix Biol， 2020， 91-92： 109-116. doi:10.1016/j.matbio.2020.03.010
10 SAWAKI D， CZIBIK G， PINI M， et al. Visceral Adipose Tissue Drives Cardiac Aging Through Modulation of Fibroblast Senescence by Osteopontin Production［J］. Circulation， 2018， 138（8）： 809-822. doi:10.1161/circulationaha.117.031358
11 LIU X， BURKE R M， LIGHTHOUSE J K， et al. p53 Regulates the Extent of Fibroblast Proliferation and Fibrosis in Left Ventricle Pressure Overload［J］. Circ Res， 2023， 133（3）： 271-287. doi:10.1161/circresaha.121.320324
12 YEGANEH A， ALIBHAI F J， TOBIN S W， et al. Age-related defects in autophagy alter the secretion of paracrine factors from bone marrow mononuclear cells［J］. Aging （Albany NY）， 2021， 13（11）： 14687-14708. doi:10.18632/aging.203127
13 LI J， LI S H， WU J， et al. Young Bone Marrow Sca-1 Cells Rejuvenate the Aged Heart by Promoting Epithelial-to-Mesenchymal Transition［J］. Theranostics， 2018， 8（7）： 1766-1781. doi:10.7150/thno.22788
14 WANG Y， QIN W Y， WANG Q， et al. Young Sca-1（+） bone marrow stem cell-derived exosomes preserve visual function via the miR-150-5p/MEKK3/JNK/c-Jun pathway to reduce M1 microglial polarization［J］. J Nanobiotechnology， 2023， 21（1）： 194. doi:10.1186/s12951-023-01944-w
15 朱国松， 王广治， 王开伟. 骨髓Sca-1间充质干细胞对肺移植后急性肺损伤的影响［J］. 实用医学杂志， 2020，36（22）：3065-3068.
16 ZHOU H， BIAN Z Y， ZONG J， et al. Stem cell antigen 1 protects against cardiac hypertrophy and fibrosis after pressure overload［J］. Hypertension， 2012， 60（3）： 802-809. doi:10.1161/hypertensionaha.112.198895
17 BAILEY B， FRANSIOLI J， GUDE N. A， et al. Sca-1 knockout impairs myocardial and cardiac progenitor cell function［J］. Circ Res， 2012， 111（6）： 750-760. doi:10.1161/circresaha.112.274662
18 LI S H， SUN Z， BRUNT K. R， et al. Reconstitution of aged bone marrow with young cells repopulates cardiac-resident bone marrow-derived progenitor cells and prevents cardiac dysfunction after a myocardial infarction［J］. Eur Heart J， 2013， 34（15）： 1157-1167. doi:10.1093/eurheartj/ehs072
19 GUO Q Y， YANG J Q， FENG X X， et al. Regeneration of the heart： from molecular mechanisms to clinical therapeutics［J］. Mil Med Res， 2023， 10（1）： 18. doi:10.1186/s40779-023-00452-0
20 MENG X， WANG H， SONG X， et al. The potential role of senescence in limiting fibrosis caused by aging［J］. J Cell Physiol， 2020， 235（5）： 4046-4059. doi:10.1002/jcp.29313
21 SHIKATANI E A， WANG T， DINGWELL L S， et al. GDF5 deficiency prevents cardiac rupture following acute myocardial infarction in mice［J］. Cardiovasc Pathol， 2024， 68： 107581. doi:10.1016/j.carpath.2023.107581
22 ZHAO X， BIAN R， WANG F， et al. GDF-5 promotes epidermal stem cells proliferation via Foxg1-cyclin D1 signaling［J］. Stem Cell Res Ther， 2021， 12（1）： 42. doi:10.1186/s13287-020-02106-7
23 DESHMUKH T， CHONG J J H. Therapeutic Angiogenesis Using Growth Factors After Myocardial Infarction： From Recombinant Proteins to Gene Therapies and Beyond［J］. Heart Lung Circ， 2023， 32（7）： 798-807. doi:10.1016/j.hlc.2023.05.018
24 MALINAUSKAS T， PEER T V， BISHOP B， et al. Repulsive guidance molecules lock growth differentiation factor 5 in an inhibitory complex［J］. Proc Natl Acad Sci U S A， 2020， 117（27）： 15620-15631. doi:10.1073/pnas.2000561117
25 WENG P W， YADAV V K， PIKATAN N W， et al. Novel NFκB Inhibitor SC75741 Mitigates Chondrocyte Degradation and Prevents Activated Fibroblast Transformation by Modulating miR-21/GDF-5/SOX5 Signaling［J］. Int J Mol Sci， 2021， 22（20）：11082. doi:10.3390/ijms222011082
Options
Outlines

/

〈 〉