The roles of mechanosensitive ion channels and associated downstream MAPK signaling pathways in PDLC mechanotransduction
Autor: | Yongchu Pan, Lin Wang, Chi Zhang, Yun Shen, Shuyu Guo, Lian Sun |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
MAPK/ERK pathway Cancer Research Spider Venoms Mechanotransduction Cellular Biochemistry Ion Channels Mice 0302 clinical medicine Phosphorylation Mechanotransduction Child mitogen-activated protein kinase pathway Cells Cultured Mice Inbred BALB C biology Chemistry Articles Piezo1 Cell biology periodontal ligament cells Oncology RANKL 030220 oncology & carcinogenesis Intercellular Signaling Peptides and Proteins Molecular Medicine Female Mechanosensitive channels transient receptor potential cation channel subfamily V member 4 Signal transduction TRPV4 Cytochalasin D Adolescent MAP Kinase Signaling System Periodontal Ligament Protein Array Analysis TRPV Cation Channels Real-Time Polymerase Chain Reaction 03 medical and health sciences Genetics Animals Humans Molecular Biology Ion channel mechanotransduction Osteoblasts Macrophage Colony-Stimulating Factor RANK Ligand PIEZO1 030104 developmental biology Cyclooxygenase 2 biology.protein |
Zdroj: | Molecular Medicine Reports |
ISSN: | 1791-3004 1791-2997 |
Popis: | The present study aimed to investigate whether the cytoskeleton, the Piezo1 ion channel and the transient receptor potential cation channel subfamily V member 4 (TRPV4) ion channel are equally functional in the mechanotransduction of periodontal ligament cells (PDLCs) and to reveal the interplay of these mechanically sensitive ion channels (MSCs). Human PDLCs (hPDLCs) were pretreated with cytochalasin D (the inhibitor of actin polymerization), GsMTx4 (the antagonist of Piezo1) and GSK205 (the antagonist of TRPV4), and then subjected to periodic mechanical loading. The expression levels of macrophage colony stimulating factor (M‑CSF), receptor activator of NF‑κB ligand (RANKL) and cyclooxygenase‑2 (COX2) in hPDLCs were detected via western blotting. Osteoblast mineralization induction capacity of the hPDLCs was also studied and the mitogen‑activated protein kinase (MAPK) expression profile was determined via protein microarray. The expression of Piezo1 and TRPV4 in the PDLCs was significantly increased at 8 h after loading. These differences in expression were accompanied by increased expression of M‑CSF, RANKL and COX2. Compared with the control group, key PDLC biomarkers were suppressed after mechanical loading following treatment with the inhibitors of Piezo1 (GsMTx4) and TRPV4 (GSK205). The phosphorylated‑MAPK protein array showed differential biomarker profiles among all groups. The present study suggested that both MSCs and the cytoskeleton participated as mechanical sensors, and did so independently in hPDLC mechanotransduction. Furthermore, the Piezo1 ion channel may transmit mechanical signals via the ERK signaling pathway; however, the TRPV4 channel may function via alternative signaling pathways. |
Databáze: | OpenAIRE |
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