Molecular mechanisms linking wound inflammation and fibrosis: knockdown of osteopontin leads to rapid repair and reduced scarring

The Journal of Experimental Medicine
Ryoichi MoriPaul Martin

Abstract

Previous studies of tissue repair have revealed osteopontin (OPN) to be up-regulated in association with the wound inflammatory response. We hypothesize that OPN may contribute to inflammation-associated fibrosis. In a series of in vitro and in vivo studies, we analyze the effects of blocking OPN expression at the wound, and determine which inflammatory cells, and which paracrine factors from these cells, may be responsible for triggering OPN expression in wound fibroblasts. Delivery of OPN antisense oligodeoxynucleotides into mouse skin wounds by release from Pluronic gel decreases OPN protein levels at the wound and results in accelerated healing and reduced granulation tissue formation and scarring. To identify which leukocytic lineages may be responsible for OPN expression, we cultured fibroblasts in macrophage-, neutrophil-, or mast cell-conditioned media (CM), and found that macrophage- and mast cell-secreted factors, specifically platelet-derived growth factor (PDGF), induced fibroblast OPN expression. Correspondingly, Gleevec, which blocks PDGF receptor signaling, and PDGF-Rbeta-neutralizing antibodies, inhibited OPN induction by macrophage-CM. These studies indicate that inflammation-triggered expression of OPN both hi...Continue Reading

References

Nov 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·S E LynchH N Antoniades
Apr 21, 1995·Annals of the New York Academy of Sciences·W T Butler
Apr 29, 1998·The Journal of Clinical Investigation·L LiawB L Hogan
Jun 28, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ryoichi MoriNaofumi Mukaida
Feb 13, 2003·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Eric I EgoziLuisa A Dipietro
Jul 5, 2003·Current Biology : CB·Paul MartinScott R McKercher
Nov 19, 2004·Biochemical Pharmacology·Sung Hee LeeDong Hwan Sohn
Jan 5, 2005·The Journal of Clinical Investigation·Jeremy S DuffieldJohn P Iredale
Mar 1, 2005·American Journal of Respiratory and Critical Care Medicine·Yoshinori AonoSaburo Sone
Mar 25, 2005·Journal of Cell Science·Elizabeth G Canty, Karl E Kadler
Jul 12, 2005·American Journal of Physiology. Renal Physiology·Christos Chatziantoniou, Jean-Claude Dussaule
Oct 6, 2005·Trends in Cell Biology·Paul Martin, S Joseph Leibovich
Jan 5, 2006·Critical Reviews in Immunology·Michael P KeaneJohn A Belperio
Mar 29, 2006·Journal of Burn Care & Research : Official Publication of the American Burn Association·Rodney K ChanDennis P Orgill
Jul 29, 2006·The Journal of Investigative Dermatology·Anuj SharmaRadha K Maheshwari
Nov 23, 2006·Cytokine & Growth Factor Reviews·Mohamed K El-TananiPhilip S Rudland
Apr 26, 2007·The Journal of Biological Chemistry·Daria LealiMarco Presta

❮ Previous
Next ❯

Citations

May 11, 2010·European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery·Benjamin J HerdrichKenneth W Liechty
May 7, 2011·Expert Reviews in Molecular Medicine·Susan R Rittling
Jul 12, 2011·Expert Reviews in Molecular Medicine·Timothy J Koh, Luisa Ann DiPietro
Jul 17, 2008·Nature Reviews. Molecular Cell Biology·Matthias Schäfer, Sabine Werner
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Antigoni TriantafyllopoulouLionel B Ivashkiv
Jul 10, 2012·The Journal of Biological Chemistry·Irena PastarMarjana Tomic-Canic
Mar 4, 2014·Advances in Wound Care·Anca Sindrilaru, Karin Scharffetter-Kochanek
May 7, 2011·Journal of Gastroenterology and Hepatology·Devanshi SethChristopher P Day
May 12, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Qianli YuDouglas F Larson
Sep 5, 2009·American Journal of Respiratory and Critical Care Medicine·Farshid N RouhaniBernadette R Gochuico
Nov 5, 2008·The Journal of Clinical Investigation·Sharon D RicardoAllison A Eddy
Dec 30, 2009·The Journal of Clinical Investigation·Chien-hui LiaoIssei Komuro
Sep 21, 2013·The Journal of Clinical Investigation·Amanda S MacLeodWendy L Havran
Sep 16, 2010·Theoretical Biology & Medical Modelling·Maria-Angeles AllerJaime Arias
Jan 25, 2013·Arthritis Research & Therapy·Ornella J RulloBetty P Tsao
Sep 4, 2009·Journal of Cell Science·Tanya J Shaw, Paul Martin
Nov 5, 2011·Yi chuan = Hereditas·Zun-Bao WangWei Zheng
Jul 5, 2011·Annual Review of Cell and Developmental Biology·Kevin J Sonnemann, William M Bement
Jul 11, 2014·The American Journal of Pathology·Ryoichi MoriIsao Shimokawa
Oct 3, 2009·Journal of Cell Communication and Signaling·Susan Amanda LundMarta Scatena
Dec 10, 2013·Journal of Cell Communication and Signaling·Charles N PagelEleanor J Mackie
Oct 8, 2014·Equine Veterinary Journal·V MiragliottaC L Theoret
May 31, 2015·Advanced Drug Delivery Reviews·Siew-Min OngSiew-Cheng Wong
Dec 15, 2015·Immunobiology·Raquel Alves CostaCláudia Rocha Carvalho
Jul 3, 2013·Journal of the American College of Surgeons·Rami A KamelEdward J Caterson
Aug 31, 2016·Burns and Trauma·Zhensen ZhuEdward E Tredget
Dec 20, 2011·Journal of the American Academy of Dermatology·Christos ProfyrisIsabel Do Vale
Sep 6, 2011·Trends in Molecular Medicine·James A StefaterJeremy S Duffield
Oct 4, 2011·The Journal of Surgical Research·Cedric HunterHoward Levinson

❮ Previous
Next ❯

Methods Mentioned

BETA
antisense oligodeoxynucleotides
biopsy
transmission electron microscopy
PCR
lavage

Software Mentioned

Openlab
Improvision
Image J

Related Concepts

Related Feeds

Antisense Oligonucleotides: ND

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.