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 JCDSA  Vol.5 No.4 , December 2015
Modulation of a Specific Pattern of microRNAs, Including miR-29a, miR-30a and miR-34a, in Cultured Human Skin Fibroblasts, in Response to the Application of a Biofunctional Ingredient that Protects against Cellular Senescence in Vitro
Abstract: Skin aging is a process of structural and compositional remodeling that can be manifested by wrinkling and sagging. Remarkably, the dermis plays a dominant role in the aging process. Recent studies suggest that microRNAs are implicated in the regulation of gene expression during aging. However, studies about age-related microRNAs and how they modulate skin aging remain limited. In the present work, a complex of hydrolyzed natural yeast proteins (Saccharomyces cerevisiae) and hydrolyzed natural soya bean was developed and showed the ability to modulate the expression of telomere-binding protein TRF2, which is a key factor for telomere protection and to prevent cellular senescence in vitro and DNA damage. The aim of the study was to identify microRNAs specifically modulated after application of the ingredient complex to cultured fibroblasts, and their possible involvement in remodeling of the human extracellular matrix and fibroblast senescence. Consequently, human skin fibroblasts were cultured and treated with 1% of the ingredient complex for 48 h before analyzing microRNA modulation by RT-qPCR. The use of bioinformatics allowed us to predict the target genes for modulated microRNAs. Results show that the ingredient complex modulated a pattern of microRNAs including the down-regulation of miR-29a-3p, miR-30a-5p and miR-34a-5p, which are associated with fibroblast senescence and remodeling of the human dermal extracellular matrix. In conclusion, our results indicate that miR-29a-3p, miR-30a-5p and miR-34a-5p possibly represent key microRNAs that impact human fibroblast senescence and remodeling of the dermal extracellular matrix.
Cite this paper: Yan, X. , Serre, C. , Bergeron, L. , Mur, L. , Busuttil, V. , Botto, J. and Domloge, N. (2015) Modulation of a Specific Pattern of microRNAs, Including miR-29a, miR-30a and miR-34a, in Cultured Human Skin Fibroblasts, in Response to the Application of a Biofunctional Ingredient that Protects against Cellular Senescence in Vitro. Journal of Cosmetics, Dermatological Sciences and Applications, 5, 332-342. doi: 10.4236/jcdsa.2015.54040.
References

[1]   Jung, H.J. and Suh, Y. (2012) MicroRNA in Aging: From Discovery to Biology. Current Genomics, 13, 548-557.
http://dx.doi.org/10.2174/138920212803251436

[2]   Smith-Vikos, T. and Slack, F.J. (2012) MicroRNAs and Their Roles in Aging. Journal of Cell Science, 125, 7-17.
http://dx.doi.org/10.1242/jcs.099200

[3]   Botto, J.M., Busuttil, V., Labarrade, F., Serre, C., Bergeron, L., Capallere, C. and Domloge, N. (2015) MicroRNAs in Skin Physiology. In: Gadberry, R.J., Epstein, H. and Botto, J.-M., Eds., Cosmetic Industry Approaches to Epigenetics and Molecular Biology (Harrys Cosmeticology 9th Edition), Chemical Publishing Company, Revere, MA, 940-1189.

[4]   Engels, B.M. and Hutvagner, G. (2006) Principles and Effects of microRNA-Mediated Post-Transcriptional Gene Regulation. Oncogene, 25, 6163-6169.
http://dx.doi.org/10.1038/sj.onc.1209909

[5]   Zhang, X., Azhar, G. and Wei, J.Y. (2012) The Expression of microRNA and microRNA Clusters in the Aging Heart. PLoS One, 7, e34688.
http://dx.doi.org/10.1371/journal.pone.0034688

[6]   Zhao, X., Huang, Y., Wang, Y., Chen, P., Yu, Y. and Song, Z. (2013) MicroRNA Profile Comparison of the Corneal Endothelia of Young and Old Mice: Implications for Senescence of the Corneal Endothelium. Molecular Vision, 19, 1815-1825.

[7]   Kwekel, J.C., Vijay, V., Desai, V.G., Moland, C.L. and Fuscoe, J.C. (2015) Age and Sex Differences in Kidney microRNA Expression during the Life Span of F344 Rats. Biology of Sex Differences, 6, 1.
http://dx.doi.org/10.1186/s13293-014-0019-1

[8]   Zhang, L., Li, J. and Zhou, K. (2009) Chelating and Radical Scavenging Activities of Soy Protein Hydrolysates Prepared from Microbial Proteases and Their Effect on Meat Lipid Peroxidation. Bioresource Technology, 101, 2084-2089.
http://dx.doi.org/10.1016/j.biortech.2009.11.078

[9]   Imbert, I., Botto, J.M., Dal Farra, C. and Domloge, N. (2012) Modulation of Telomere Binding Proteins: A Future Area of Research for Skin Protection and Anti-Aging Target. Journal of Cosmetic Dermatology, 11, 162-166.
http://dx.doi.org/10.1111/j.1473-2165.2012.00611.x

[10]   De Lange, T. (2005) Shelterin: The Protein Complex That Shapes and Safeguards Human Telomeres. Genes & Development, 19, 2100-2110.
http://dx.doi.org/10.1101/gad.1346005

[11]   Stewart, J.A., Chaiken, M.F., Wang, F. and Price, C.M. (2012) Maintaining the End: Roles of Telomere Proteins in End-Protection, Telomere Replication and Length Regulation. Mutation Research, 730, 12-19.
http://dx.doi.org/10.1016/j.mrfmmm.2011.08.011

[12]   Bergeron, L., Lebleu, A., Court, E., Busuttil, V., Botto, J.M. and Domloge, N. (2012) Modulating TRF2 Expression Preserves Telomere Integrity and Prevents DNA DSBs, during Aging. Journal of Investigative Dermatology, 132, S51-S64.

[13]   Dweep, H., Sticht, C., Pandey, P. and Gretz, N. (2011) miRWalk—Database: Prediction of Possible miRNA Binding Sites by “Walking” the Genes of Three Genomes. Journal of Biomedical Informatics, 44, 839-847.
http://dx.doi.org/10.1016/j.jbi.2011.05.002

[14]   Vlachos, I.S., Paraskevopoulou, M.D., Karagkouni, D., Georgakilas, G., Vergoulis, T., Kanellos, I., Anastasopoulos, I.L., Maniou, S., Karathanou, K., Kalfakakou, D., Fevgas, A., Dalamagas, T. and Hatzigeorgiou, A.G. (2015) DIANA-TarBase v7.0: Indexing More than Half a Million Experimentally Supported miRNA:mRNA Interactions. Nucleic Acids Research, 43, D153-D159.
http://dx.doi.org/10.1093/nar/gku1215

[15]   Xiao, F., Zuo, Z., Cai, G., Kang, S., Gao, X. and Li, T. (2009) miRecords: An Integrated Resource for MicroRNA-Target Interactions. Nucleic Acids Research, 37, D105-D110.
http://dx.doi.org/10.1093/nar/gkn851

[16]   Lewis, B.P., Burge, C.B. and Bartel, D.P. (2005) Conserved Seed Pairing, Often Flanked by Adenosines, Indicates That Thousands of Human Genes Are MicroRNA Targets. Cell, 120, 15-20.
http://dx.doi.org/10.1016/j.cell.2004.12.035

[17]   Bonifacio, L. and Jarstfer, M. (2010) miRNA Profile Associated with Replicative Senescence, Extended Cell Culture, and Ectopic Telomerase Expression in Human Foreskin Fibroblasts. PLoS ONE, 5, e12519.
http://dx.doi.org/10.1371/journal.pone.0012519

[18]   Marasa, B., Srikantan, S., Martindale, J., Kim, M.M., Lee, E.K., Gorospe, M. and Abdelmohsen, K. (2010) MicroRNA Profiling in Human Diploid Fibroblasts Uncovers miR-519 Role in Replicative Senescence. Aging, 2, 333-343.

[19]   Martinez, I., Cazalla, D., Almstead, L., Steitz, J.A. and DiMaio, D. (2011) miR-29 and miR-30 Regulate B-Myb Expression during Cellular Senescence. Proceedings of the National Academy of Sciences of the United States of America, 108, 522-527.
http://dx.doi.org/10.1073/pnas.1017346108

[20]   Maes, O.C., Sarojini, H. and Wang, E. (2009) Stepwise Up-Regulation of MicroRNA Expression Levels from Replicating to Reversible and Irreversible Growth Arrest States in WI-38 Human Fibroblasts. Journal of Cellular Physiology, 221, 109-119.
http://dx.doi.org/10.1002/jcp.21834

[21]   Suh, E.J., Remillard, M.Y., Legesse-Miller, A., Johnson, E.L., Lemons, J.M., Chapman, T.R., Forman, J.J., Kojima, M., Silberman, E.S. and Coller, H.A. (2012) A MicroRNA Network Regulates Proliferative Timing and Extracellular Matrix Synthesis during Cellular Quiescence in Fibroblasts. Genome Biology, 13, R121.
http://dx.doi.org/10.1186/gb-2012-13-12-r121

[22]   Tomé, M., Lopez-Romero, P., Albo, C., Sepúlveda, J.C., Fernández-Gutiérrez, B., Dopazo, A., Bernad, A. and González, MA. (2011) miR-335 Orchestrates Cell Proliferation, Migration and Differentiation in Human Mesenchymal Stem Cells. Cell Death & Differentiation, 18, 985-995.
http://dx.doi.org/10.1038/cdd.2010.167

[23]   Olivieri, F., Rippo, M.R., Monsurrò, V., Salvioli, S., Capri, M., Procopio, A.D. and Franceschi, C. (2013) MicroRNAs Linking Inflamm-Aging, Cellular Senescence and Cancer. Ageing Research Reviews, 12, 1056-1068.
http://dx.doi.org/10.1016/j.arr.2013.05.001

[24]   He, L., He, X., Lim, L.P., de Stanchina, E., Xuan, Z., Liang, Y., Xue, W., Zender, L., Magnus, J., Ridzon, D., Jackson, A.L., Linsley, P.S., Chen, C., Lowe, S.W., Cleary, M.A. and Hannon, G.J. (2007) A MicroRNA Component of the p53 Tumour Suppressor Network. Nature, 447, 1130-1134.
http://dx.doi.org/10.1038/nature05939

[25]   Yang, J., Chen, D., He, Y., Meléndez, A., Feng, Z., Hong, Q., Bai, X., Li, Q., Cai, G., Wang, J. and Chen, X. (2013) miR-34 Modulates Caenorhabditis elegans Lifespan via Repressing the Autophagy Gene atg9. AGE, 35, 11-22.
http://dx.doi.org/10.1007/s11357-011-9324-3

[26]   Li, N., Muthusamy, S., Liang, R., Sarojini, H. and Wang, E. (2011) Increased Expression of miR-34a and miR-93 in Rat Liver during Aging, and Their Impact on the Expression of Mgst1 and Sirt1. Mechanisms of Ageing and Development, 132, 75-85.
http://dx.doi.org/10.1016/j.mad.2010.12.004

[27]   Liu, N., Landreh, M., Cao, K., Abe, M., Hendriks, G.J., Kennerdell, J.R., Zhu, Y., Wang, L.S. and Bonini, N.M. (2012) The MicroRNA miR-34 Modulates Ageing and Neurodegeneration in Drosophila. Nature, 482, 519-523.
http://dx.doi.org/10.1038/nature10810

[28]   Seeger, T. and Boon, R.A. (2015) MicroRNAs in Cardiovascular Aging. The Journal of Physiology.
http://dx.doi.org/10.1113/JP270557

[29]   Yamakuchi, M. and Lowenstein, C.J. (2009) miR-34, SIRT1 and p53: The Feedback Loop. Cell Cycle, 8, 712-715.
http://dx.doi.org/10.4161/cc.8.5.7753

[30]   Lopez-Otin, C., Blasco, M.A., Partridge, L., Serrano, M. and Kroemer, G. (2013) The Hallmarks of Aging. Cell, 153, 1194-1217.
http://dx.doi.org/10.1016/j.cell.2013.05.039

[31]   Ugalde, A.P., Espanol, Y. and Lopez-Otin, C. (2011) Micromanaging Aging with miRNAs: New Messages from the Nuclear Envelope. Nucleus, 2, 549-555.
http://dx.doi.org/10.4161/nucl.2.6.17986

[32]   Feliciano, A., Sánchez-Sendra, B., Kondoh, H. and Lleonart, M.E. (2011) MicroRNAs Regulate Key Effector Pathways of Senescence. Journal of Aging Research, 2011, Article ID: 205378.

 
 
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