The effects of GPR40 agonists on hair growth are mediated by ANGPTL4 - 28/03/23


Abstract |
GPR40 is found primarily in pancreatic β cells, and is well known to regulate insulin secretion. Despite numerous studies on GPR40, the role and functions of GPR40 related to hair growth are not yet known. The current study investigated hair growth promoting effect of the GPR40 agonists and its mechanism of action using various bio-informatics tools, in vitro and animal experiments. GPR40 may affect the hair cycle, according to clustering and Gene Set Enrichment Analysis (GSEA). Hair growth effect of GPR40 was validated by telogen-to-anagen transition and vibrissae organ culture in the mouse. GPR40 was predominantly expressed in the outer root sheath (ORS) in anagen stage, suggesting that ORS cell is the target of GPR40 agonists. To investigate the mechanism of action for GPR40 agonists’ hair growth effect, Gene Ontology (GO) enrichment analysis was performed and it revealed that GPR40 agonists were associated with angiogenesis. ANGPTL4, known for promoting angiogenesis, was highly up-regulated after GPR40 agonists treatment in the hORS cells, and also increased the proliferation and migration. Furthermore, GPR40 agonists promoted hair growth by inducing angiogenesis via ANGPTL4 in the animal experiment. GPR40 agonists activated MAPK and peroxisome proliferator-activated receptors (PPARγ) pathway in hORS cells, while the inhibition of MAPK pathway attenuated ANGPTL4 expression. Finally, GPR40 agonists increased hair growth via autocrine effects in the ORS cells, and induced angiogenesis through paracrine effects by upregulating ANGPTL4 via p38 and PPARγ pathways. As a result, GPR40 agonists have potential as a therapeutic drug for hair loss treatment.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | Despite numerous studies on GPR40, the role and functions of GPR40 related to hair growth have yet to be reported. |
• | GPR40 is predominantly expressed in the outer root sheath cell during the anagen stage of the hair cycle, indicating that the ORS cell is the target of GPR40. |
• | GPR40 agonists accelerated the telogen-to-anagen transition and increased the hair length in vibrissae organ culture. |
• | ANGPTL4 was significantly increased after GPR40 agonists treatment and mediated hair growth via p38 and PPARγ. |
Abbreviations : GPR40, GPCR, ORS, PPARγ, MAPK, ANGPTL4, HF, GO, GSEA, PUFAs, AA, DEG, FPKM, TPM, GMT
Keywords : GPR40, Hair growth, PPARγ, ANGPTL4, Angiogenesis, Anagen induction
Plan
Vol 161
Article 114509- mai 2023 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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