Antagonizing Effects of Aspartic Acid against Ultraviolet A-Induced Downregulation of the Stemness of Human Adipose Tissue-Derived Mesenchymal Stem Cells

Kwangseon Jung; Jae Youl Cho; Young-Jin Soh; Jienny Lee; Seoung Woo Shin; Sunghee Jang; Eunsun Jung; Min Hee Kim; Jongsung Lee

doi:10.1371/journal.pone.0124417

Antagonizing Effects of Aspartic Acid against Ultraviolet A-Induced Downregulation of the Stemness of Human Adipose Tissue-Derived Mesenchymal Stem Cells

PLoS One. 2015 Apr 24;10(4):e0124417. doi: 10.1371/journal.pone.0124417. eCollection 2015.

Authors

Kwangseon Jung¹, Jae Youl Cho², Young-Jin Soh³, Jienny Lee⁴, Seoung Woo Shin⁵, Sunghee Jang⁶, Eunsun Jung⁵, Min Hee Kim⁷, Jongsung Lee⁸

Affiliations

¹ Department of Convergence Biomedical Science & Engineering, Eulji University, Seongnam City, Gyunggi Do, Republic of Korea; Skincure Life Science Institute, Seongnam City, Gyunggi Do, Republic of Korea.
² Department of Genetic Engineering, Sungkyunkwan University, Suwon-Si, Gyeonggi-Do, Republic of Korea.
³ Department of Dermatological Health Management, College of Health Science, Eulji University, Seongnam City, Gyunggi Do, Korea.
⁴ Viral Disease Division, Animal and Plant Quarantine Agency, 175 Anyang-Ro, Manan-Gu, Anyang-Si, Gyeonggi-Do, Republic of Korea.
⁵ Biospectrum Life Science Institute, Seongnam City, Gyunggi Do, Republic of Korea.
⁶ Department of Senior Healthcare, BK21 plus program, Graduated school, Eulji University, Seongnam City, Gyunggi Do, Republic of Korea.
⁷ Department of Physical Therapy, College of Health Science, Eulji University, Seongnam City, Gyunggi Do, Republic of Korea.
⁸ Department of Convergence Biomedical Science & Engineering, Eulji University, Seongnam City, Gyunggi Do, Republic of Korea; Department of Senior Healthcare, BK21 plus program, Graduated school, Eulji University, Seongnam City, Gyunggi Do, Republic of Korea.

Abstract

Ultraviolet A (UVA) irradiation is responsible for a variety of changes in cell biology. The purpose of this study was to investigate effects of aspartic acid on UVA irradiation-induced damages in the stemness properties of human adipose tissue-derived mesenchymal stem cells (hAMSCs). Furthermore, we elucidated the UVA-antagonizing mechanisms of aspartic acid. The results of this study showed that aspartic acid attenuated the UVA-induced reduction of the proliferative potential and stemness of hAMSCs, as evidenced by increased proliferative activity in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and upregulation of stemness-related genes OCT4, NANOG, and SOX2 in response to the aspartic acid treatment. UVA-induced reduction in the mRNA level of hypoxia-inducible factor (HIF)-1α was also significantly recovered by aspartic acid. In addition, the antagonizing effects of aspartic acid against the UVA effects were found to be mediated by reduced production of PGE2 through the inhibition of JNK and p42/44 MAPK. Taken together, these findings show that aspartic acid improves reduced stemness of hAMSCs induced by UVA and its effects are mediated by upregulation of HIF-1α via the inhibition of PGE2-cAMP signaling. In addition, aspartic acid may be used as an antagonizing agent to mitigate the effects of UVA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipose Tissue / cytology
Arabidopsis Proteins / genetics
Arabidopsis Proteins / metabolism
Aspartic Acid / pharmacology*
Cell Proliferation / drug effects
Cell Proliferation / radiation effects
Cells, Cultured
Cyclic AMP / biosynthesis
Dinoprostone / biosynthesis
Down-Regulation / drug effects
Down-Regulation / radiation effects
Humans
Hypoxia-Inducible Factor 1, alpha Subunit / genetics
Intramolecular Transferases / genetics
Intramolecular Transferases / metabolism
MAP Kinase Signaling System / drug effects
MAP Kinase Signaling System / radiation effects
Mesenchymal Stem Cells / drug effects*
Mesenchymal Stem Cells / metabolism
Mesenchymal Stem Cells / radiation effects*
Transcription Factor AP-1 / antagonists & inhibitors
Ultraviolet Rays / adverse effects*

Substances

Arabidopsis Proteins
HIF1A protein, human
Hypoxia-Inducible Factor 1, alpha Subunit
Transcription Factor AP-1
Aspartic Acid
Cyclic AMP
Intramolecular Transferases
marneral synthase, Arabidopsis
Dinoprostone

Grants and funding

This study was supported by a grant from the Korean Health Technology R & D Project, Ministry of Health and Welfare, Republic of Korea (Grant Number: HN13C0072). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Co-author Kwangseon Jung is employed by Skincure Life Science Institute. Skincure Life Science Institute provided support in the form of salary for author KJ, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the ‘author contributions’ section. Co-author Eunsun Jung is employed by Biospectrum Life Science Institute. Biospectrum Life Science Institute provided support in the form of salary for author EJ, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.