• angiotensin-converting enzyme;
  • development;
  • fetus;
  • skin;
  • stem cell


Background  Recent evidence has revealed that angiotensin-converting enzyme (ACE) participates in cutaneous wound healing and contributes to the pathophysiological process of some skin diseases. However, little is known about the role of ACE in epidermis morphogenesis during development.

Objective  To clarify the expression pattern of ACE during embryonic development of human skin.

Methods  Skin samples were obtained from aborted fetuses at different gestational ages and from healthy individuals. Localization of ACE, together with β1-integrin, keratin 19 (K19) and p63 was examined by immunofluorescence and immunohistochemical staining.

Results  In human fetal skin, at 11–13 weeks of gestation, ACE-positive cells were observed in the primitive epidermis. As the fetuses developed, ACE-positive cells appeared in all the epidermal layers. From 21 weeks of gestation, ACE expression was largely restricted to the basal layer of the fetal epidermis. In contrast, ACE-positive cells were found only in the adult skin basal layer which harbours epidermal stem cells. To explore the possible link between ACE and epidermal stem cells, we further examined the expression of β1-integrin, K19 and p63, the putative markers for epidermal stem cells. Consistent with the results of ACE expression, from 21 weeks of gestation, the expression of β1-integrin, K19 and p63 was mainly confined to the basal layer. Immunofluorescent double labelling revealed that ACE-positive cells substantially overlapped with β1-integrin-, K19- and p63-positive cells.

Conclusions  Our results suggest that ACE may play a role in human epidermis morphogenesis during fetal life and serve as an unrecognized marker for keratinocyte progenitor cells.