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Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model
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Published on: September 7, 2013

PGC-1 coactivators regulate MITF and the tanning response.

Jonathan Shoag1, Rizwan Haq, Mingfeng Zhang

  • 1Cardiovascular Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.

Molecular Cell
|December 4, 2012
PubMed
Summary
This summary is machine-generated.

PPAR-gamma coactivators (PGC)-1α and PGC-1β regulate skin tanning by activating MITF, a key factor in melanin production. Genetic variations in PGC-1β influence human tanning ability and melanoma risk.

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Area of Science:

  • Molecular biology
  • Dermatology
  • Genetics

Background:

  • Melanocytes produce pigment for skin tanning and UV protection.
  • Melanogenesis is triggered by α-MSH, which activates MITF in melanocytes.

Purpose of the Study:

  • To investigate the role of PPAR-γ coactivators (PGC)-1α and PGC-1β in the melanogenic pathway.
  • To determine if PGC-1 coactivators are involved in human tanning responses and melanoma susceptibility.

Main Methods:

  • Assessed PGC-1α and PGC-1β expression and protein stability following α-MSH stimulation.
  • Analyzed MITF promoter activity and melanogenic gene expression in response to PGC-1 manipulation.
  • Examined PGC-1α overexpression effects in cell culture and transgenic models.
  • Conducted polymorphism studies to correlate PGC-1β gene variants with tanning ability and melanoma risk.

Main Results:

  • α-MSH signaling robustly induces PGC-1α expression and stabilizes PGC-1α and PGC-1β proteins.
  • PGC-1α and PGC-1β activate the MITF promoter, with their expression correlating with MITF levels in melanoma.
  • Inhibition of PGC-1s blocked α-MSH-induced MITF and melanogenic gene expression.
  • PGC-1α overexpression promoted pigment formation in vitro and in vivo.
  • Genetic variations in PGC-1β were linked to tanning ability and melanoma protection.

Conclusions:

  • PGC-1α and PGC-1β are essential regulators of the melanogenic system in melanocytes.
  • These coactivators mediate α-MSH-induced MITF activation and pigment production.
  • PGC-1 coactivators represent novel targets for understanding and potentially modulating human tanning and skin cancer risk.