The Growth Differentiation Factor 11 is Involved in Skin Fibroblast Ageing and is Induced by a Preparation of Peptides and Sugars Derived from Plant Cell Cultures

Abstract

Ageing is a complex and progressive phenomenon, during which the accumulation of morphological and chemical changes seriously compromises the capacity of the cells to proliferate and fulfil their biological tasks. The increase in the average age of the world population, associated with a higher occurrence of age-related diseases, is prompting scientific research to look for new strategies and molecular targets that may help in alleviating age-related phenotypes. Growth factors, responsible for modulating several aging markers in many tissues and organs, represent valuable targets to fight age-associated dysfunctions. The growth differentiation factor GDF11, a TGF-β family member, has been associated with the maintenance of youth phenotypes in different human tissues and organs, and in the skin has been related to an inhibition of the inflammatory response. We investigated the role of GDF11 in skin dermal fibroblasts, and we observed that its expression and activity were reduced in fibroblasts deriving from adult donors compared to neonatal ones. The main effect of GDF11 was the induction of collagen I and III, in both neonatal and adult fibroblasts, by triggering Smad signalling in a TGF-β-like fashion. Moreover, by analysing a number of plant extracts having GDF11 inducing activity, we found that a peptide/sugar preparation, obtained from Lotus japonicus somatic embryo cultures, was capable of restoring GDF11 expression in older fibroblasts and to activate the synthesis of collagen I, collagen III and periostin, an important protein involved in collagen assembly.

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Acknowledgements

We want to thank prof. Maria Antonietta Bellisario (University of Salerno, Italy) and Dr. Lieve Declercq for their critical reading of the article and useful hints. The study was supported by the grant Horizon 2020—PON 2014/2020.

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Correspondence to Fabio Apone.

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Figures S1

Supplementary material 1. . 1D [1H] (A) and 1D [13C] (B) spectra of the LJSEC extract in methanol-d4 recorded at 600 MHz. Spectral regions containing sugars resonances are indicated by the red bars. Detailed NMR analysis of the sugar fraction was rather complicated by the extensive spectral overlaps in the region containing most of carbohydrates proton resonances (between 3 and 4 ppm) (panel A). However, anomeric proton signals resonating in a less crowded spectral region, around 5 ppm, could be easily recognized. Figures S2. [1H, 13C] HMQC spectrum of the LjSEC extract in methanol-d4 recorded at 400 MHz. Signals from the anomeric -CH- groups in alpha- and beta-glucose forms are indicated. Figures S3 2D [1H-1H] TOCSY spectrum of LjSEC extract. The peaks arising from amino-acids and sugars are indicated. Leucine, isoleucine, and aspartic acid which, according to the amino acid analysis, were among the most abundant residues in the mixture, could be recognized in the 2D [1H, 1H] spectrum. (PDF 343 KB)

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Tito, A., Barbulova, A., Zappelli, C. et al. The Growth Differentiation Factor 11 is Involved in Skin Fibroblast Ageing and is Induced by a Preparation of Peptides and Sugars Derived from Plant Cell Cultures. Mol Biotechnol 61, 209–220 (2019). https://doi.org/10.1007/s12033-019-00154-w

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Keywords

  • Skin ageing
  • Growth differentiation factor 11
  • Neonatal and adult fibroblasts
  • Collagen induction
  • Peptide/sugar extract