| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Articles in PresS, published online ahead of print December 20, 2001
Am J Physiol Lung Cell Mol Physiol, 10.1152/ajplung.00315.2001
Submitted on August 8, 2001
Accepted on December 18, 2001
1 Pulmonary and Critical Care Division, New England Medical Center, Boston, MA, USA; Physiology, Tufts University, Boston, MA, USA
2 Pulmonary and Critical Care Division, New England Medical Center, Boston, MA, USA
3 Physiology, Tufts University, Boston, MA, USA
* To whom correspondence should be addressed. E-mail: cochran{at}cochranlab.org.
Airway remodeling, as manifested by an increase in airway smooth muscle (ASM) mass, mucous gland hyperplasia, and sub-epithelial fibrosis contributes to the fixed obstruction seen in some asthmatic patients. Here, we have investigated whether the Jak-STAT pathway contributes to PDGF stimulated mitogenesis of human airway smooth cells (HASMC). PDGF treatment of quiescent HASMC resulted in the rapid tyrosine phosphorylation and DNA binding of STAT1 and STAT3. This phosphorylation was blocked by inhibition of Src and Jak2 kinases. In addition, STAT activation by PDGF was found to be redox-dependent. Moreover, PDGF-induced thymidine uptake was completely blocked by pretreatment of HASMC with the STAT kinase inhibitors AG490, SU6656, and PP2. Interestingly, the Jak kinase pathway was required for HASMC mitogenesis independently of MAPK activation. Inhibition of the Src and Jak kinases blocked PDGF-stimulated gene expression of the STAT target genes cyclin D1 and c-myc. These results indicate that the Jak-STAT pathway contributes to PDGF-induced mitogenesis and thus this pathway may be important in the airway remodeling seen in some asthmatic patients.
This article has been cited by other articles:
|
|
 |
|
  E. A. Goncharova, D. A. Goncharov, G. Damera, O. Tliba, Y. Amrani, R. A. Panettieri Jr., and V. P. Krymskaya Signal Transducer and Activator of Transcription 3 Is Required for Abnormal Proliferation and Survival of TSC2-Deficient Cells: Relevance to Pulmonary Lymphangioleiomyomatosis Mol. Pharmacol., October 1, 2009; 76(4): 766 - 777. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Seidel, I. Merfort, J. M. Hughes, B. G. G. Oliver, M. Tamm, and M. Roth Dimethylfumarate inhibits NF-{kappa}B function at multiple levels to limit airway smooth muscle cell cytokine secretion Am J Physiol Lung Cell Mol Physiol, August 1, 2009; 297(2): L326 - L339. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Janssen Asthma therapy: how far have we come, why did we fail and where should we go next? Eur. Respir. J., January 1, 2009; 33(1): 11 - 20. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Simeone-Penney, M. Severgnini, L. Rozo, S. Takahashi, B. H. Cochran, and A. R. Simon PDGF-induced human airway smooth muscle cell proliferation requires STAT3 and the small GTPase Rac1 Am J Physiol Lung Cell Mol Physiol, April 1, 2008; 294(4): L698 - L704. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A M Sutcliffe and A J Knox Muscling into cystic fibrosis airways Thorax, March 1, 2005; 60(3): 181 - 182. [Full Text] [PDF]
|
|
|
|
|
|
M. Severgnini, S. Takahashi, L. M. Rozo, R. J. Homer, C. Kuhn, J. W. Jhung, G. Perides, M. Steer, P. M. Hassoun, B. L. Fanburg, et al. Activation of the STAT pathway in acute lung injury Am J Physiol Lung Cell Mol Physiol, June 1, 2004; 286(6): L1282 - L1292. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Kataoka, I. Matsumura, S. Ezoe, S. Nakata, E. Takigawa, Y. Sato, A. Kawasaki, T. Yokota, K. Nakajima, A. Felsani, et al. Reciprocal Inhibition between MyoD and STAT3 in the Regulation of Growth and Differentiation of Myoblasts J. Biol. Chem., November 7, 2003; 278(45): 44178 - 44187. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
