New therapeutic targets in dermatoporosis

J Nutr Health Aging. 2012 Apr;16(4):285-8. doi: 10.1007/s12603-012-0041-0.


Dermatoporosis is a novel term proposed to describe the chronic cutaneous insufficiency/fragility syndrome characterized by an extreme skin atrophy. Dermatoporosis is principally due to chronological aging and long-term and unprotected sun exposure, but it may also result from the chronic use of topical and systemic corticosteroids. We have recently proposed a membrane organelle, hyalurosome, composed of molecules involved in hyaluronate (HA) metabolism and cell signaling in the keratinocytes, such as principal HA receptor CD44, heparin-binding epidermal growth factor (HB-EGF), HB-EGF receptor erbB1 and HA synthase 3 (HAS3), which is functionally defective in dermatoporosis and may be a target for intervention. Several lines of evidence suggest that hyalurosome is located in keratinocyte filopodia, thin, actin-rich plasma membrane protrusions implicated in cell motility. We have recently shown that keratinocyte filopodia are downregulated by corticosteroids in vitro. Intermediate size HA fragments (HAFi) inhibited the downregulation of filopodia induced by corticosteroids. Topical HAFi prevented the skin atrophy induced by topical corticosteroids in mice without interfering with their anti-inflammatory effect. Topical treatment with HAFi 1% of atrophic forearm skin of dermatoporosis patients for 1 month resulted in a significant clinical improvement and induced the expression of hyalurosome molecules. Topical retinaldehyde (RAL) and HAFi showed a synergy in HA production and pro-HB-EGF expression in mouse skin and in the correction of skin atrophy in dermatoporosis patients. Uncovering the molecular mechanisms implicating hyalurosome seems to be crucial to better understand the pathogenesis of dermatoporosis and to develop new therapeutic strategies.

MeSH terms

  • Adrenal Cortex Hormones / adverse effects
  • Adrenal Cortex Hormones / antagonists & inhibitors
  • Aged
  • Aged, 80 and over
  • Aging*
  • Animals
  • Atrophy
  • Cell Movement
  • Down-Regulation / drug effects
  • Drug Synergism
  • Epidermis / metabolism
  • Epidermis / pathology
  • Female
  • Glucuronosyltransferase / metabolism
  • Heparin-binding EGF-like Growth Factor
  • Humans
  • Hyaluronan Synthases
  • Hyaluronic Acid / metabolism
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Keratinocytes / cytology
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Male
  • Mice
  • Middle Aged
  • Pseudopodia / metabolism
  • Retinaldehyde / pharmacology
  • Skin / drug effects
  • Skin / pathology*
  • Skin Diseases / drug therapy*
  • Skin Diseases / physiopathology


  • Adrenal Cortex Hormones
  • HBEGF protein, human
  • Hbegf protein, mouse
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins
  • Hyaluronic Acid
  • Glucuronosyltransferase
  • HAS3 protein, human
  • Has3 protein, mouse
  • Hyaluronan Synthases
  • Retinaldehyde