MicroRNA-29a Exhibited Pro-Angiogenic and Anti-Fibrotic Features to Intensify Human Umbilical Cord Mesenchymal Stem Cells—Renovated Perfusion Recovery and Preventing against Fibrosis from Skeletal Muscle Ischemic Injury

Autor: Chun-Wun Lu, Yun-Ting Kao, Yi-Yung Hung, Ching-Jen Wang, Wen-Hong Su, Pei-Chin Chuang, Shun-Hung Tseng, Chia-Yu Ou, Ching-Chin Tsai
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
Angiogenesis
umbilical cord mesenchymal stem cells
Umbilical Cord
lcsh:Chemistry
Mice
angiogenesis
0302 clinical medicine
Fibrosis
Ischemia
Medicine
lcsh:QH301-705.5
Spectroscopy
Tube formation
General Medicine
Computer Science Applications
medicine.anatomical_structure
030220 oncology & carcinogenesis
Heterografts
Stem cell
Neovascularization
Physiologic
Mesenchymal Stem Cell Transplantation
Catalysis
Article
Inorganic Chemistry
03 medical and health sciences
Muscular Diseases
Animals
Humans
Physical and Theoretical Chemistry
Muscle
Skeletal
Molecular Biology
business.industry
Organic Chemistry
Mesenchymal stem cell
fibrosis
skeletal muscle injury
Skeletal muscle
Mesenchymal Stem Cells
Tissue inhibitor of metalloproteinase
medicine.disease
Transplantation
MicroRNAs
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Cancer research
microrna-29a
business
Zdroj: International Journal of Molecular Sciences, Vol 20, Iss 23, p 5859 (2019)
International Journal of Molecular Sciences
Volume 20
Issue 23
ISSN: 1422-0067
Popis: This study was conducted to elucidate whether microRNA-29a (miR-29a) and/or together with transplantation of mesenchymal stem cells isolated from umbilical cord Wharton&rsquo
s jelly (uMSCs) could aid in skeletal muscle healing and putative molecular mechanisms. We established a skeletal muscle ischemic injury model by injection of a myotoxin bupivacaine (BPVC) into gastrocnemius muscle of C57BL/6 mice. Throughout the angiogenic and fibrotic phases of muscle healing, miR-29a was considerably downregulated in BPVC-injured gastrocnemius muscle. Overexpressed miR-29a efficaciously promoted human umbilical vein endothelial cells proliferation and capillary-like tube formation in vitro, crucial steps for neoangiogenesis, whereas knockdown of miR-29a notably suppressed those endothelial functions. Remarkably, overexpressed miR-29a profitably elicited limbic flow perfusion and estimated by Laser Dopple. MicroRNA-29a motivated perfusion recovery through abolishing the tissue inhibitor of metalloproteinase (TIMP)-2, led great numbers of pro-angiogenic matrix metalloproteinases (MMPs) to be liberated from bondage of TIMP, thus reinforced vascular development. Furthermore, engrafted uMSCs also illustrated comparable effect to restore the flow perfusion and augmented vascular endothelial growth factors-A, -B, and -C expression. Notably, the combination of miR29a and the uMSCs treatments revealed the utmost renovation of limbic flow perfusion. Amplified miR-29a also adequately diminished the collagen deposition and suppressed broad-wide miR-29a targeted extracellular matrix components expression. Consistently, miR-29a administration intensified the relevance of uMSCs to abridge BPVC-aggravated fibrosis. Our data support that miR-29a is a promising pro-angiogenic and anti-fibrotic microRNA which delivers numerous advantages to endorse angiogenesis, perfusion recovery, and protect against fibrosis post injury. Amalgamation of nucleic acid-based strategy (miR-29a) together with the stem cell-based strategy (uMSCs) may be an innovative and eminent strategy to accelerate the healing process post skeletal muscle injury.
Databáze: OpenAIRE
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