GDF11 enhances therapeutic efficacy of mesenchymal stem cells for myocardial infarction via YME1L-mediated OPA1 processing.

Stem Cells Translational Medicine
Yun ZhaoHong Yu

Abstract

Growth differentiation factor 11 (GDF11) has been shown to promote stem cell activity, but little is known about the effect of GDF11 on viability and therapeutic efficacy of cardiac mesenchymal stem cells (MSCs) for cardiac injury. To understand the roles of GDF11 in MSCs, mouse heart-derived MSCs were transduced with lentiviral vector carrying genes for both GDF11 and green fluorescent protein (GFP) (MSCsLV-GDF11 ) or cultured with recombinant GDF11 (MSCsrGDF11 ). Either MSCsrGDF11 or MSCs LV-GDF11 displayed less cell apoptosis and better paracrine function, as well as preserved mitochondrial morphology and function under hypoxic condition as compared with control MSCs. GDF11 enhanced phosphorylation of Smad2/3, which upregulated expression of YME1L, a mitochondria protease that balances OPA1 processing. Inhibitors of TGF-β receptor (SB431542) or Smad2/3 (SIS3) attenuated the effects of GDF11 on cell viability, mitochondrial function, and expression of YME1L. Transplantation of MSCsGDF11 into infarct heart resulted in improved cell survival and retention, leading to more angiogenesis, smaller scar size, and better cardiac function in comparison with control MSCs. GDF11 enhanced viability and therapeutic efficiency of MSCs by p...Continue Reading

References

Jun 20, 2007·Biochemical and Biophysical Research Communications·Yao Liang TangM Ian Phillips
Nov 2, 2013·Cell Death & Disease·Y RuanZ Song
Mar 13, 2014·The Journal of Cell Biology·Ruchika AnandThomas Langer
May 24, 2015·Cell Metabolism·Marc A EgermanDavid J Glass
Feb 14, 2016·Heart Failure Reviews·José Marín-García, Alexander T Akhmedov
Mar 12, 2016·Trends in Molecular Medicine·Fabian Sanchis-GomarAlejandro Lucia
May 18, 2016·Journal of Cell Science·Thomas MacVicar, Thomas Langer
Aug 10, 2016·Molecular Therapy : the Journal of the American Society of Gene Therapy·Wen MeiMin Liu
Dec 23, 2016·Nature Reviews. Cardiology·David A BrownMihai Gheorghiade
Feb 9, 2017·Stem Cells Translational Medicine·Kan WangJian'an Wang
Feb 9, 2017·EMBO Reports·Manon RosselinNicolas Demaurex
Mar 28, 2017·Biochimica Et Biophysica Acta. Molecular Cell Research·Jinliang NanJian'an Wang
Jun 22, 2017·Cell Reports·Valentina Del DottoClaudia Zanna
Aug 1, 2018·Frontiers in Cellular Neuroscience·Lu LuBing-Qiao Zhao
Sep 11, 2018·Journal of Cranio-maxillo-facial Surgery : Official Publication of the European Association for Cranio-Maxillo-Facial Surgery·V RempelM Kreppel
Feb 23, 2019·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·You WuZhong-Qiu Lu

❮ Previous
Next ❯

Citations

Oct 8, 2020·International Journal of Molecular Sciences·Kamila RaziyevaArman Saparov
Aug 14, 2021·Stem Cell Research & Therapy·Chi ZhangHong Yu

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
transfection
ELISA
immunoprecipitation
PCR
electrophoresis
electron microscopy
ChIP
GTPase

Software Mentioned

Jaspar
ImageJ
GraphPad
Prism

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis