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Tytuł pozycji:

The fibrillin-1 RGD motif posttranscriptionally regulates ERK1/2 signaling and fibroblast proliferation via miR-1208.

Tytuł:
The fibrillin-1 RGD motif posttranscriptionally regulates ERK1/2 signaling and fibroblast proliferation via miR-1208.
Autorzy:
Zhang RM; Faculty of Medicine and Health Sciences, Department of Anatomy and Cell Biology, McGill University, Montreal, Canada.
Zeyer KA; Faculty of Medicine and Health Sciences, Department of Anatomy and Cell Biology, McGill University, Montreal, Canada.
Odenthal N; Department of Natural Science, University of Lübeck, Lübeck, Germany.
Zhang Y; Faculty of Medicine and Health Sciences, Department of Anatomy and Cell Biology, McGill University, Montreal, Canada.
Reinhardt DP; Faculty of Medicine and Health Sciences, Department of Anatomy and Cell Biology, McGill University, Montreal, Canada.; Faculty of Dentistry, McGill University, Montreal, Canada.
Źródło:
FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2021 May; Vol. 35 (5), pp. e21598.
Typ publikacji:
Journal Article; Research Support, Non-U.S. Gov't
Język:
English
Imprint Name(s):
Publication: 2020- : [Bethesda, Md.] : Hoboken, NJ : Federation of American Societies for Experimental Biology ; Wiley
Original Publication: [Bethesda, Md.] : The Federation, [c1987-
MeSH Terms:
RNA Processing, Post-Transcriptional*
Fibrillin-1/*metabolism
Fibroblasts/*cytology
MicroRNAs/*genetics
Mitogen-Activated Protein Kinase 1/*genetics
Mitogen-Activated Protein Kinase 3/*genetics
Oligopeptides/*metabolism
Cell Proliferation ; Cells, Cultured ; Fibrillin-1/genetics ; Fibroblasts/metabolism ; Humans ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; Oligopeptides/genetics
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Grant Information:
PJT-162099 Canada CIHR
Contributed Indexing:
Keywords: ERK1/2 signaling; RGD; fibrillin-1; fibroblasts; miR-1208; proliferation
Substance Nomenclature:
0 (FBN1 protein, human)
0 (Fibrillin-1)
0 (MicroRNAs)
0 (Oligopeptides)
78VO7F77PN (arginyl-glycyl-aspartic acid)
EC 2.7.11.24 (MAPK1 protein, human)
EC 2.7.11.24 (MAPK3 protein, human)
EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
Entry Date(s):
Date Created: 20210419 Date Completed: 20210719 Latest Revision: 20210719
Update Code:
20240104
DOI:
10.1096/fj.202100282R
PMID:
33871068
Czasopismo naukowe
Fibrillin-1 is an extracellular matrix protein which contains one conserved RGD integrin-binding motif. It constitutes the backbone of microfibrils in many tissues, and mutations in fibrillin-1 cause various connective tissue disorders. Although it is well established that fibrillin-1 interacts with several RGD-dependent integrins, very little is known about the associated intracellular signaling pathways. Recent published evidence identified a subset of miRNAs regulated by fibrillin-1 RGD-cell adhesion, with miR-1208 among the most downregulated. The present study shows that the downregulated miR-1208 controls fibroblast proliferation. Inhibitor experiments revealed that fibrillin-1 RGD suppressed miR-1208 expression via c-Src kinase and the downstream JNK signaling. Bioinformatic prediction and experimental target sequence validation demonstrated four miR-1208 binding sites on the ERK2 mRNA and one on the MEK1 mRNA. ERK2 and MEK1 are critical proliferation-promoting kinases. Decreased miR-1208 levels elevated the total and phosphorylated ERK1/2 and MEK1/2 protein levels and the phosphorylated to total ERK1/2 ratio. Together, the data demonstrate a novel outside-in signaling mechanism explaining how fibrillin-1 RGD-cell binding regulates fibroblast proliferation.
(© 2021 Federation of American Societies for Experimental Biology.)

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