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The opioid growth factor, [Met5]-enkephalin, inhibits DNA synthesis during recornification of mouse tail skin
R P Wilson1, P J McLaughlin, C M Lang
1Department of Comparative Medicine, College of Medicine, The Pennsylvania State University, Hershey 17033-2390, USA. rpw4@psu.edu
Abstract:
Opioid peptides serve as tonically active negative growth regulators in renewing and regenerating epithelia. To examine the involvement of opioids in renewal of the stratum corneum after tape stripping of tail skin, C57BL/6 J mice were given systemic injections of the potent opioid antagonist, naltrexone (NTX, 20 mg/kg i.p.) following injury. Blockade of opioid-receptor interaction by NTX for 4 h resulted in an elevation of 36-66% in basal cell DNA synthesis measured 24 h after injury. Injection of the endogenous opioid peptide, [Met5]-enkephalin (OGF, 10 mg/kg i.p.) 4 h before termination, suppressed radiolabelled thymidine incorporation in the basal cell layer by 37-46% at 24 h after wounding. The magnitude of the effects on DNA synthesis of OGF, but not NTX, depended on the timing of administration with respect to injury. OGF maximally depressed basal cell labelling (72%) when given 16 h after tape stripping. Concomitant administration of naloxone (10 mg/kg) with OGF blocked the inhibition of DNA synthesis; naloxone alone at the dosage utilized had no effect on cell labelling. Both OGF and its receptor, OGFr, were detected by immunocytochemistry in the basal and suprabasal cell layers, but not the cornified layer of tape stripped and uninjured tail skin. These results indicate: (a) a native opioid peptide and its receptor are expressed in epidermal cells of injured and uninjured mouse tail skin; (b) removal of the stratum corneum by tape stripping does not disrupt the function of the endogenous opioid growth system; (c) the proliferative response to wounding of the tail is tonically inhibited by the receptor-mediated action of an endogenous opioid peptide; and (d) DNA synthesis by basal cells can be elevated by disrupting opioid peptide receptor interactions.
Insights
Endogenous opioid peptides inhibit skin cell growth. Blocking opioid receptors or administering opioid peptides affects DNA synthesis in regenerating mouse tail skin, revealing a role in wound healing.
Area of Science:
- Dermatology
- Molecular Biology
- Cell Biology
Background:
- Opioid peptides are known negative regulators of epithelial growth and regeneration.
- The role of endogenous opioids in the specific context of stratum corneum renewal following injury remains to be fully elucidated.
Purpose of the Study:
- To investigate the involvement of endogenous opioid peptides in the renewal of the stratum corneum after tape stripping injury in mouse tail skin.
- To determine the effects of opioid receptor blockade and stimulation on basal cell DNA synthesis post-injury.
Main Methods:
- Mice (C57BL/6 J) were subjected to tape stripping of tail skin to induce injury.
- Systemic injections of opioid antagonist naltrexone (NTX) or opioid peptide [Met5]-enkephalin (OGF) were administered at various time points post-injury.
- DNA synthesis was measured using radiolabeled thymidine incorporation.
- Immunocytochemistry was used to detect OGF and its receptor (OGFr) in epidermal cells.
Main Results:
- Naltrexone administration elevated basal cell DNA synthesis by 36-66% 24 hours after injury, indicating opioid-mediated inhibition.
- [Met5]-enkephalin suppressed DNA synthesis by 37-46% at 24 hours post-wounding.
- The effect of OGF on DNA synthesis was time-dependent, with maximal inhibition (72%) observed when administered 16 hours post-injury.
- Naloxone blocked OGF-induced inhibition, confirming receptor-mediated effects.
- OGF and OGFr were detected in basal and suprabasal epidermal layers of both injured and uninjured skin.
Conclusions:
- A native opioid peptide and its receptor are present in mouse tail skin epidermis.
- The endogenous opioid system functions to tonically inhibit the proliferative response to wounding in tail skin.
- Disrupting opioid peptide-receptor interactions can enhance basal cell DNA synthesis, suggesting a therapeutic potential for wound healing.
