Critical roles of the nuclear receptor PPARbeta (peroxisome-proliferator-activated receptor beta) in skin wound healing.
The PPARs (peroxisome-proliferator-activated receptors) alpha, beta/delta and gamma belong to the nuclear hormone receptor superfamily. While all three receptors are undetectable in adult mouse interfollicular epidermis, PPARbeta expression and activity is strongly re-activated by inflammatory stimuli during epidermal injury. The pro-inflammatory cytokine TNFalpha (tumour necrosis factor alpha) stimulates transcription of the PPARbeta gene via an activator protein-1 site in its promoter and it also triggers the production of PPARbeta ligands in keratinocytes. This increase of PPARbeta activity in these cells up-regulates the expression of integrin-linked kinase and 3-phosphoinositide-dependent kinase-1, which phosphorylates protein kinase B-alpha (Akt1). The resulting increase in Akt1 activity suppresses apoptosis and ensures the presence of a sufficient number of viable keratinocytes at the wound margin for re-epithelialization. Together, these observations reveal that PPARbeta takes on multiple roles and contributes favourably to the process of wound closure.
Tan
N S
NS
Centre Intégratif de Génomique, Université de Lausanne, Bâtiment de biologie, CH-1015 Lausanne, Switzerland.
Michalik
L
L
Di-Poï
N
N
Desvergne
B
B
Wahli
W
W
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism*; D014945:Wound Healing
D011518:Proto-Oncogene Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt