Hepatoma-derived growth factor enhances osteoblastic transformation of rat aortic vascular smooth muscle cells in vitro.
Animals
Biomarkers
/ metabolism
Cell Line, Transformed
Cell Movement
/ drug effects
Cell Proliferation
/ drug effects
Cells, Cultured
Core Binding Factor Alpha 1 Subunit
/ metabolism
Gene Silencing
/ drug effects
Intercellular Signaling Peptides and Proteins
/ pharmacology
Kinetics
Muscle, Smooth, Vascular
/ cytology
Myocytes, Smooth Muscle
/ cytology
Osteoblasts
/ cytology
Osteogenesis
/ drug effects
Osteopontin
/ metabolism
Proto-Oncogene Proteins c-akt
/ metabolism
Rats, Sprague-Dawley
Up-Regulation
/ drug effects
p38 Mitogen-Activated Protein Kinases
/ metabolism
Arteriosclerosis
Signaling transduction
Vascular calcification
Vascular remodeling
Journal
Life sciences
ISSN: 1879-0631
Titre abrégé: Life Sci
Pays: Netherlands
ID NLM: 0375521
Informations de publication
Date de publication:
01 Sep 2020
01 Sep 2020
Historique:
received:
24
02
2020
revised:
02
06
2020
accepted:
09
06
2020
pubmed:
14
6
2020
medline:
1
9
2020
entrez:
14
6
2020
Statut:
ppublish
Résumé
Vascular smooth muscle cells (VSMCs) are important regulators of vascular functions and their conversion to osteoblasts is a key to development of vascular calcification. This study aimed to characterize in vitro effect of hepatoma-derived growth factor (HDGF) on phenotypic conversion of cultured aortic VSMCs into osteoblast-like cells. Cell proliferation and migration assays were used to examine cell behaviors. Western blotting, alkaline phosphatase activity and calcium staining were used to evaluate osteoblastic marker expression and function, respectively. Recombinant HDGF treatment enhanced VSMC growth and motility. Treatment of osteogenic medium (OM) increased expression of not only HDGF but also osteoblastic markers, including Runx2 and osteopontin (OPN), while VSMC marker α-smooth muscle actin (α-SMA) declined. Coincidentally, HDGF and OM treatment alone stimulated signaling activities in both PI3K/Akt and MAPK pathways. Conversely, inhibition of Akt and p38 significantly blocked the OM-upregulated HDGF, Runx2, and OPN expression and NF-κB phosphorylation, but did not reversed the α-SMA downregulation, implicating the involvement of Akt and p38 activities in the osteoblastic transformation of VSMCs. Small interfering RNA-mediated HDGF gene silencing effectively prevented the Runx2 and OPN upregulation, alkaline phosphatase activation, and calcium deposition, but did not affect the α-SMA levels in the transformed cells, supporting the involvement of HDGF in regulation of Runx2 and OPN expression. In conclusion, in synergism with other osteogenic factor, HDGF may promote the progression of osteobastic transformation of VSMCs via Akt and p38 signaling pathways and contribute to vascular calcification in arteriosclerosis. HDGF (PubChem CID:); LY294002 (PubChem CID: 3973); PD98059 (PubChem CID: 4713); SB203580 (PubChem CID: 176155); SB431542 (PubChem CID: 4521392); SP600125 (PubChem CID: 8515); Wortmannin (PubChem CID: 312145).
Identifiants
pubmed: 32534036
pii: S0024-3205(20)30714-1
doi: 10.1016/j.lfs.2020.117964
pii:
doi:
Substances chimiques
Biomarkers
0
Core Binding Factor Alpha 1 Subunit
0
Intercellular Signaling Peptides and Proteins
0
hepatoma-derived growth factor
0
Osteopontin
106441-73-0
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
p38 Mitogen-Activated Protein Kinases
EC 2.7.11.24
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
117964Informations de copyright
Copyright © 2020. Published by Elsevier Inc.