Protease-activated receptor type 1 (PAR1) increases CEMP1 gene expression through MAPK/ERK pathway

Autor(es)

Emanuel Silva Rovai ^[1] ; Tomaz Alves ^[2] ; Letícia Miquelitto Gasparoni ^[3] ; Bruno Nunes de França ^[4] ; Carla Renata Sipert ^[5] ; Alpdogan Kantarci ^[6] ; Marinella Holzhausen ^[7]

Afiliação do(s) autor(es)

^[1] Universidade de Taubaté. School of Dentistry. Periodontics Research Division - Brasil

^[2] Universidade de São Paulo. School of Dentistry. Departament of Periodontics - Brasil

^[3] Universidade de São Paulo. School of Dentistry. Departament of Periodontics - Brasil

^[4] Universidade Cruzeiro do Sul. Dental School. Department of Dentistry - Brasil

^[5] Universidade de São Paulo. School of Dentistry. Departament of Periodontics - Brasil

^[6] The Forsyth Institute - Estados Unidos

^[7] Universidade de São Paulo. School of Dentistry. Departament of Periodontics - Brasil

• Tipo de documento: Artigo Científico
• Fonte: Brazilian Oral Research; v. 36, 2022-04-15.

Resumo

Abstract: PAR1 is a G-coupled protein receptor that regulates several cellular metabolism processes, including differentiation and proliferation of osteogenic and cementogenic related cells and our group previously demonstrated the regenerative potential of PAR1 in human periodontal ligament stem cells (hPDLSCs). In this study, we hypothesized that PAR1 regulates the cementogenic differentiation of hPDLSCs. Our goal was to identify the intracellular signaling pathway underlying PAR1 activation in hPDSLC differentiation. hPDLSCs were isolated using the explant technique. Cells were cultured in an osteogenic medium (OST) (α-MEM, 15% fetal bovine serum, L-glutamine, penicillin, streptomycin, amphotericin B, dexamethasone, and beta-glycerophosphate). The hPDLSCs were treated with a specific activator of PAR1 (PAR1 agonist) and blockers of the MAPK/ERK and PI3K pathways for 2 and 7 days. The gene expression of CEMP1 was assessed by RT-qPCR. The activation of PAR1 by its agonist peptide led to an increase in CEMP1 gene expression when compared with OST control. MAPK/ERK blockage abrogated the upregulation of CEMP1 gene expression induced by PAR1 agonist (p < 0.05). PI3K blockage did not affect the gene expression of CEMP1 at any experimental time (p > 0.05). We concluded that CEMP1 gene expression increased by PAR1 activation is MAPK/ERK-dependent and PI3K independent, suggesting that PAR1 may regulate cementogenetic differentiation of hPDLSCs. (AU)

• Processo FAPESP: 18/13818-5 - Efeito da ativação do Receptor Ativado por Protease do tipo 1 (PAR1) sobre a atividade osteogênica em membranas de células-tronco do ligamento periodontal humano. ensaio in vivo
• Beneficiário: Tomaz Alves da Silva Neto
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 17/23158-0 - Efeito da ativação do receptor ativado por protease do tipo 1 (par1) sobre a atividade osteogênica em membranas de células-tronco do ligamento periodontal humano
• Beneficiário: Marinella Holzhausen Caldeira
• Modalidade de apoio: Auxílio à Pesquisa - Regular