Resistin Enhances Monocyte Chemoattractant Protein-1 Production in Human Synovial Fibroblasts and Facilitates Monocyte Migration.
3' Untranslated Regions
Antagomirs
/ metabolism
Cell Movement
/ drug effects
Cells, Cultured
Chemokine CCL2
/ chemistry
Fibroblasts
/ cytology
Gene Expression
/ drug effects
Humans
MicroRNAs
/ antagonists & inhibitors
Monocytes
/ cytology
Osteoarthritis
/ metabolism
Phosphatidylinositol 3-Kinases
/ genetics
Phosphoinositide-3 Kinase Inhibitors
Proto-Oncogene Proteins c-akt
/ antagonists & inhibitors
RNA Interference
RNA, Small Interfering
/ metabolism
Recombinant Proteins
/ biosynthesis
Resistin
/ genetics
Signal Transduction
/ drug effects
Synovial Membrane
/ cytology
TOR Serine-Threonine Kinases
/ antagonists & inhibitors
MCP-1
Monocyte migration
Osteoarthritis
Resistin
Journal
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
ISSN: 1421-9778
Titre abrégé: Cell Physiol Biochem
Pays: Germany
ID NLM: 9113221
Informations de publication
Date de publication:
2019
2019
Historique:
received:
15
11
2018
accepted:
05
03
2019
entrez:
8
3
2019
pubmed:
8
3
2019
medline:
16
3
2019
Statut:
ppublish
Résumé
The adipocyte-secreting adipokine, resistin, may play a critical role in the modulation of inflammatory diseases. Migration and infiltration of mononuclear cells into inflammatory sites are critical events during the development of osteoarthritis (OA). Monocyte chemoattractant protein-1 (MCP-1), also known as chemokine ligand 2 (CCL2), plays a critical role in the regulation of monocyte migration and infiltration. In this study, we show how resistin promotes MCP-1 expression in OA synovial fibroblasts and monocyte migration. We used qPCR to detect MCP-1 and miRNA expression. THP-1 migration was investigated by Transwell assay. The Western blotting was used to examine the resistinmediated signaling pathways. Resistin activated the phosphatidylinositol-3-kinase (PI3K), Akt and mammalian target of rapamycin (mTOR) signaling pathways, while PI3K, Akt and mTOR inhibitors or small interfering RNAs diminished resistin-induced MCP-1 expression and monocyte migration. We also demonstrate that resistin stimulates MCP-1mediated monocyte migration by suppressing microRNA (miR)-33a and miR-33b via the PI3K, Akt and mTOR signaling pathways. These results provide new insights into the mechanisms of resistin action that may have therapeutic implications for patients with OA.
Sections du résumé
BACKGROUND/AIMS
OBJECTIVE
The adipocyte-secreting adipokine, resistin, may play a critical role in the modulation of inflammatory diseases. Migration and infiltration of mononuclear cells into inflammatory sites are critical events during the development of osteoarthritis (OA). Monocyte chemoattractant protein-1 (MCP-1), also known as chemokine ligand 2 (CCL2), plays a critical role in the regulation of monocyte migration and infiltration. In this study, we show how resistin promotes MCP-1 expression in OA synovial fibroblasts and monocyte migration.
METHODS
METHODS
We used qPCR to detect MCP-1 and miRNA expression. THP-1 migration was investigated by Transwell assay. The Western blotting was used to examine the resistinmediated signaling pathways.
RESULTS
RESULTS
Resistin activated the phosphatidylinositol-3-kinase (PI3K), Akt and mammalian target of rapamycin (mTOR) signaling pathways, while PI3K, Akt and mTOR inhibitors or small interfering RNAs diminished resistin-induced MCP-1 expression and monocyte migration. We also demonstrate that resistin stimulates MCP-1mediated monocyte migration by suppressing microRNA (miR)-33a and miR-33b via the PI3K, Akt and mTOR signaling pathways.
CONCLUSION
CONCLUSIONS
These results provide new insights into the mechanisms of resistin action that may have therapeutic implications for patients with OA.
Substances chimiques
3' Untranslated Regions
0
Antagomirs
0
Chemokine CCL2
0
MicroRNAs
0
Phosphoinositide-3 Kinase Inhibitors
0
RNA, Small Interfering
0
Recombinant Proteins
0
Resistin
0
MTOR protein, human
EC 2.7.1.1
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
408-420Subventions
Organisme : Taiwan's Ministry of Science and Technology
ID : 105-2320-B-039-015-MY3
Pays : Taiwan
Organisme : China Medical University
ID : CMU106-S-27
Pays : China
Organisme : MacKay Memorial Hospital
ID : MMH-107-55, MMH-108-53
Pays : Taiwan
Organisme : Mackay Medical College
ID : MMC-1071B27
Pays : Taiwan
Informations de copyright
© Copyright by the Author(s). Published by Cell Physiol Biochem Press.
Déclaration de conflit d'intérêts
The authors have no financial or personal relationships that could inappropriately influence this research.