Human Cell

, Volume 31, Issue 1, pp 72–77 | Cite as

Age-related changes in cyclic phosphatidic acid-induced hyaluronic acid synthesis in human fibroblasts

  • Katsura Sano
  • Mari Gotoh
  • Kyoko Dodo
  • Noriaki Tajima
  • Yoshibumi Shimizu
  • Kimiko Murakami-MurofushiEmail author
Research Article


Hyaluronic acid is a major component of the extracellular matrix, which is important for skin hydration. As aging brings skin dehydration, we aimed to clarify the mRNA expression of hyaluronic acid-related proteins in human skin fibroblasts from donors of various ages (range 0.7–69 years). Previously, we reported that cyclic phosphatidic acid (cPA), a unique phospholipid mediator, stimulated the expression of HAS2 and increased hyaluronic acid synthesis in human skin fibroblasts (donor age: 3 days). In this study, we measured the mRNA expression of hyaluronic acid-related proteins: hyaluronan synthase (HAS) 1–3, hyaluronidase-1, -2, and hyaluronic acid-binding protein (versican). In addition, we tested whether cPA could increase hyaluronic acid synthesis in skin fibroblasts derived from donors of various ages. The expression of HAS1, 3, hyaluronidase-1, and -2 did not change with aging. However, the mRNA expression of versican decreased with aging. Although it is thought that the amount of hyaluronic acid in the dermis decreases with aging, the mRNA expression of HAS2 was increased. But the amount of hyaluronic acid secreted by fibroblasts did not increase with aging. This suggests that the activity and/or protein expression of HAS2 decrease with aging. Furthermore, we observed that cPA caused the increase of hyaluronic acid synthesis at any age, and this effect was increased with aging. These results suggest that aging made the fibroblasts more sensitive to cPA treatment. Therefore, cPA represents a suitable candidate for the health maintenance and improvement of the skin by increasing the level of hyaluronic acid in the dermis.


Aging Cyclic phosphatidic acid Hyaluronic acid Hyaluronan synthase Human skin fibroblasts Versican 



Bovine serum albumin




Cyclic phosphatidic acid


Cyclic adenosine monophosphate response element-binding protein


Extracellular-signal-regulated kinase


Hyaluronan synthase


Lysophosphatidic acid


LPA receptor


Messenger RNA


Phosphate-buffered saline


Polymerase chain reaction


Population doubling level


Rho/Rho-associated kinase



We thank Dr. Kazuhiko Kaji of the Nihon Pharmaceutical University for giving us the fibroblasts. This work was funded by the Grant-in-Aid for Scientific Research (KAKENHI, no. 26860144) from the Ministry of Education, Culture, Sports, Science, and Technology.

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest associated with this manuscript.


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Copyright information

© Japan Human Cell Society and Springer Japan KK 2017

Authors and Affiliations

  • Katsura Sano
    • 1
    • 2
  • Mari Gotoh
    • 1
    • 3
  • Kyoko Dodo
    • 2
  • Noriaki Tajima
    • 2
  • Yoshibumi Shimizu
    • 1
  • Kimiko Murakami-Murofushi
    • 1
    Email author
  1. 1.Endowed Research Division of Human Welfare SciencesOchanomizu UniversityTokyoJapan
  2. 2.ALBION Co., LtdTokyoJapan
  3. 3.Institute for Human Life InnovationOchanomizu UniversityTokyoJapan

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