Osteopontin Expression Is Required for Myofibroblast Differentiation
| Autor: | Yair Lenga, Christopher A. McCulloch, Aruni Shamalee Perera, Ron Zohar, Adeline Koh, Jaro Sodek |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Physiology
Phalloidin medicine.medical_treatment Collagen Type I Transforming Growth Factor beta1 Focal adhesion Mice chemistry.chemical_compound stomatognathic system Stress Fibers medicine Animals Humans Myocytes Cardiac Pseudopodia Osteopontin HMGB1 Protein RNA Small Interfering Cells Cultured Actin Mice Knockout Focal Adhesions Wound Healing biology Cell Differentiation Dermis Fibroblasts Fibrosis Actins Cell biology Fibronectin Cytokine Gene Expression Regulation chemistry biology.protein Lamellipodium Cardiology and Cardiovascular Medicine Myofibroblast |
| Zdroj: | Circulation Research. 102:319-327 |
| ISSN: | 1524-4571 0009-7330 |
| Popis: | Osteopontin (OPN) is a multifunctional cytokine that is strongly expressed in healing wounds and fibrotic lesions, both of which are characterized by the formation of myofibroblasts. We examined the role of OPN in myofibroblast differentiation induced by the profibrotic cytokine transforming growth factor-beta1. In cultured cardiac or dermal fibroblasts treated with transforming growth factor-beta1, there was a 2- to 5-fold increase in the expression of the myofibroblast markers alpha-smooth muscle actin and extradomain A fibronectin but no significant increase of these proteins in OPN-null fibroblasts. Phalloidin staining for actin filaments and immunostaining for alpha-smooth muscle actin and focal adhesion proteins showed reduced stress fibers, focal adhesions, and lamellipodia in OPN-null fibroblasts compared with wild-type cells. OPN-null fibroblasts exhibited 40% to 60% less spreading, 50% less resistance to detachment by shear force, and a approximately 3-fold reduction in collagen gel contraction. These defects were partially rescued by ectopic expression of OPN. Mass spectrometric analysis of proteins in focal adhesions formed on collagen type I beads revealed an enrichment of HMGB1 protein in wild-type cells, whereas HMGB1 was not detected in OPN-null cells. Treatment of wild-type cells with small interfering RNA to knock down OPN reduced transforming growth factor-beta1-induced alpha-smooth muscle actin and HMGB1 to levels observed in OPN-null cells. These studies demonstrate that OPN is required for the differentiation and activity of myofibroblasts formed in response to the profibrotic cytokine transforming growth factor-beta1. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|