The role of PPARγ-mediated signalling in skin biology and pathology: New targets and opportunities for clinical dermatology

Yuval Ramot, Arianna Mastrofrancesco, Emanuela Camera, Pierre Desreumaux, Ralf Paus, Mauro Picardo

Research output: Contribution to journalReview article

32 Citations (Scopus)

Abstract

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that modulate the expression of multiple different genes involved in the regulation of lipid, glucose and amino acid metabolism. PPARs and cognate ligands also regulate important cellular functions, including cell proliferation and differentiation, as well as inflammatory responses. This includes a role in mediating skin and pilosebaceous unit homoeostasis: PPARs appear to be essential for maintaining skin barrier permeability, inhibit keratinocyte cell growth, promote keratinocyte terminal differentiation and regulate skin inflammation. They also may have protective effects on human hair follicle (HFs) epithelial stem cells, while defects in PPARγ-mediated signalling may promote the death of these stem cells and thus facilitate the development of cicatricial alopecia (lichen planopilaris). Overall, however, selected PPARγ modulators appear to act as hair growth inhibitors that reduce the proliferation and promote apoptosis of hair matrix keratinocytes. The fact that commonly prescribed PPARγ-modulatory drugs of the thiazolidine-2,4-dione class can exhibit a battery of adverse cutaneous effects underscores the importance of distinguishing beneficial from clinically undesired cutaneous activities of PPARγ ligands and to better understand on the molecular level how PPARγ-regulated cutaneous lipid metabolism and PPARγ-mediated signalling impact on human skin physiology and pathology. Surely, the therapeutic potential that endogenous and exogenous PPARγ modulators may possess in selected skin diseases, ranging from chronic inflammatory hyperproliferative dermatoses like psoriasis and atopic dermatitis, via scarring alopecia and acne can only be harnessed if the complexities of PPARγ signalling in human skin and its appendages are systematically dissected.

Original languageEnglish (US)
Pages (from-to)245-251
Number of pages7
JournalExperimental Dermatology
Volume24
Issue number4
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

Dermatology
Peroxisome Proliferator-Activated Receptors
Pathology
Skin
Keratinocytes
Alopecia
Ligands
Stem cells
Skin Diseases
Hair
Modulators
Skin Physiological Phenomena
Stem Cells
Growth Inhibitors
Lichens
Hair Follicle
Acne Vulgaris
Physiology
Cell proliferation
Cell growth

Keywords

  • Hair
  • Inflammation
  • Peroxisome proliferator-activated receptors
  • Skin
  • Treatment

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

Cite this

The role of PPARγ-mediated signalling in skin biology and pathology : New targets and opportunities for clinical dermatology. / Ramot, Yuval; Mastrofrancesco, Arianna; Camera, Emanuela; Desreumaux, Pierre; Paus, Ralf; Picardo, Mauro.

In: Experimental Dermatology, Vol. 24, No. 4, 01.01.2015, p. 245-251.

Research output: Contribution to journalReview article

Ramot, Yuval ; Mastrofrancesco, Arianna ; Camera, Emanuela ; Desreumaux, Pierre ; Paus, Ralf ; Picardo, Mauro. / The role of PPARγ-mediated signalling in skin biology and pathology : New targets and opportunities for clinical dermatology. In: Experimental Dermatology. 2015 ; Vol. 24, No. 4. pp. 245-251.
@article{63d847928c024ae09545db7a82021b75,
title = "The role of PPARγ-mediated signalling in skin biology and pathology: New targets and opportunities for clinical dermatology",
abstract = "Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that modulate the expression of multiple different genes involved in the regulation of lipid, glucose and amino acid metabolism. PPARs and cognate ligands also regulate important cellular functions, including cell proliferation and differentiation, as well as inflammatory responses. This includes a role in mediating skin and pilosebaceous unit homoeostasis: PPARs appear to be essential for maintaining skin barrier permeability, inhibit keratinocyte cell growth, promote keratinocyte terminal differentiation and regulate skin inflammation. They also may have protective effects on human hair follicle (HFs) epithelial stem cells, while defects in PPARγ-mediated signalling may promote the death of these stem cells and thus facilitate the development of cicatricial alopecia (lichen planopilaris). Overall, however, selected PPARγ modulators appear to act as hair growth inhibitors that reduce the proliferation and promote apoptosis of hair matrix keratinocytes. The fact that commonly prescribed PPARγ-modulatory drugs of the thiazolidine-2,4-dione class can exhibit a battery of adverse cutaneous effects underscores the importance of distinguishing beneficial from clinically undesired cutaneous activities of PPARγ ligands and to better understand on the molecular level how PPARγ-regulated cutaneous lipid metabolism and PPARγ-mediated signalling impact on human skin physiology and pathology. Surely, the therapeutic potential that endogenous and exogenous PPARγ modulators may possess in selected skin diseases, ranging from chronic inflammatory hyperproliferative dermatoses like psoriasis and atopic dermatitis, via scarring alopecia and acne can only be harnessed if the complexities of PPARγ signalling in human skin and its appendages are systematically dissected.",
keywords = "Hair, Inflammation, Peroxisome proliferator-activated receptors, Skin, Treatment",
author = "Yuval Ramot and Arianna Mastrofrancesco and Emanuela Camera and Pierre Desreumaux and Ralf Paus and Mauro Picardo",
year = "2015",
month = "1",
day = "1",
doi = "10.1111/exd.12647",
language = "English (US)",
volume = "24",
pages = "245--251",
journal = "Experimental Dermatology",
issn = "0906-6705",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - The role of PPARγ-mediated signalling in skin biology and pathology

T2 - New targets and opportunities for clinical dermatology

AU - Ramot, Yuval

AU - Mastrofrancesco, Arianna

AU - Camera, Emanuela

AU - Desreumaux, Pierre

AU - Paus, Ralf

AU - Picardo, Mauro

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that modulate the expression of multiple different genes involved in the regulation of lipid, glucose and amino acid metabolism. PPARs and cognate ligands also regulate important cellular functions, including cell proliferation and differentiation, as well as inflammatory responses. This includes a role in mediating skin and pilosebaceous unit homoeostasis: PPARs appear to be essential for maintaining skin barrier permeability, inhibit keratinocyte cell growth, promote keratinocyte terminal differentiation and regulate skin inflammation. They also may have protective effects on human hair follicle (HFs) epithelial stem cells, while defects in PPARγ-mediated signalling may promote the death of these stem cells and thus facilitate the development of cicatricial alopecia (lichen planopilaris). Overall, however, selected PPARγ modulators appear to act as hair growth inhibitors that reduce the proliferation and promote apoptosis of hair matrix keratinocytes. The fact that commonly prescribed PPARγ-modulatory drugs of the thiazolidine-2,4-dione class can exhibit a battery of adverse cutaneous effects underscores the importance of distinguishing beneficial from clinically undesired cutaneous activities of PPARγ ligands and to better understand on the molecular level how PPARγ-regulated cutaneous lipid metabolism and PPARγ-mediated signalling impact on human skin physiology and pathology. Surely, the therapeutic potential that endogenous and exogenous PPARγ modulators may possess in selected skin diseases, ranging from chronic inflammatory hyperproliferative dermatoses like psoriasis and atopic dermatitis, via scarring alopecia and acne can only be harnessed if the complexities of PPARγ signalling in human skin and its appendages are systematically dissected.

AB - Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that modulate the expression of multiple different genes involved in the regulation of lipid, glucose and amino acid metabolism. PPARs and cognate ligands also regulate important cellular functions, including cell proliferation and differentiation, as well as inflammatory responses. This includes a role in mediating skin and pilosebaceous unit homoeostasis: PPARs appear to be essential for maintaining skin barrier permeability, inhibit keratinocyte cell growth, promote keratinocyte terminal differentiation and regulate skin inflammation. They also may have protective effects on human hair follicle (HFs) epithelial stem cells, while defects in PPARγ-mediated signalling may promote the death of these stem cells and thus facilitate the development of cicatricial alopecia (lichen planopilaris). Overall, however, selected PPARγ modulators appear to act as hair growth inhibitors that reduce the proliferation and promote apoptosis of hair matrix keratinocytes. The fact that commonly prescribed PPARγ-modulatory drugs of the thiazolidine-2,4-dione class can exhibit a battery of adverse cutaneous effects underscores the importance of distinguishing beneficial from clinically undesired cutaneous activities of PPARγ ligands and to better understand on the molecular level how PPARγ-regulated cutaneous lipid metabolism and PPARγ-mediated signalling impact on human skin physiology and pathology. Surely, the therapeutic potential that endogenous and exogenous PPARγ modulators may possess in selected skin diseases, ranging from chronic inflammatory hyperproliferative dermatoses like psoriasis and atopic dermatitis, via scarring alopecia and acne can only be harnessed if the complexities of PPARγ signalling in human skin and its appendages are systematically dissected.

KW - Hair

KW - Inflammation

KW - Peroxisome proliferator-activated receptors

KW - Skin

KW - Treatment

UR - http://www.scopus.com/inward/record.url?scp=84925965583&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84925965583&partnerID=8YFLogxK

U2 - 10.1111/exd.12647

DO - 10.1111/exd.12647

M3 - Review article

C2 - 25644500

AN - SCOPUS:84925965583

VL - 24

SP - 245

EP - 251

JO - Experimental Dermatology

JF - Experimental Dermatology

SN - 0906-6705

IS - 4

ER -