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Role of Smad2/3 and p38 MAP kinase in TGF-β1-induced epithelial-mesenchymal transition of pulmonary epithelial cells.
J Cell Physiol. 2011 May; 226(5):1248-54.JC

Abstract

Idiopathic pulmonary fibrosis is characterized by myofibroblast accumulation, extracellular matrix (ECM) remodeling, and excessive collagen deposition. ECM-producing myofibroblasts may originate from epithelial cells through epithelial to mesenchymal transition (EMT). TGF-β1 is an inducer of EMT in pulmonary epithelial cells in vitro and in vivo, though the mechanisms are unclear. We hypothesized that TGF-β1 induced EMT through Smad-dependent and -independent processes. To test this hypothesis, we studied the roles and mechanisms of TGF-β1-induced Smad and p38 mitogen-activated protein kinase (MAPK) signaling in EMT-related changes in pulmonary epithelial cells. Exposure of pulmonary epithelial 1HAEo(-) cells to TGF-β1 resulted in morphological and molecular changes of EMT over a 96-h period; loss of cell-cell contact, cell elongation, down-regulation of E-cadherin, up-regulation of fibronectin, and up-regulation of collagen I. Both Smad2/3 and p38 MAPK signaling pathways were activated by TGF-β1. However, neither Smad2/3 nor p38 MAPK were required for the down-regulation of E-cadherin, yet p38 MAPK was associated with fibronectin up-regulation. Both Smad2/3 and p38 MAPK had a role in regulation of TGF-β1-induced collagen expression. Furthermore, these data demonstrate that Smads and p38 MAPK differentially regulate EMT-related changes in pulmonary epithelial cells.

Authors+Show Affiliations

Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

20945383

Citation

Kolosova, Irina, et al. "Role of Smad2/3 and P38 MAP Kinase in TGF-β1-induced Epithelial-mesenchymal Transition of Pulmonary Epithelial Cells." Journal of Cellular Physiology, vol. 226, no. 5, 2011, pp. 1248-54.
Kolosova I, Nethery D, Kern JA. Role of Smad2/3 and p38 MAP kinase in TGF-β1-induced epithelial-mesenchymal transition of pulmonary epithelial cells. J Cell Physiol. 2011;226(5):1248-54.
Kolosova, I., Nethery, D., & Kern, J. A. (2011). Role of Smad2/3 and p38 MAP kinase in TGF-β1-induced epithelial-mesenchymal transition of pulmonary epithelial cells. Journal of Cellular Physiology, 226(5), 1248-54. https://doi.org/10.1002/jcp.22448
Kolosova I, Nethery D, Kern JA. Role of Smad2/3 and P38 MAP Kinase in TGF-β1-induced Epithelial-mesenchymal Transition of Pulmonary Epithelial Cells. J Cell Physiol. 2011;226(5):1248-54. PubMed PMID: 20945383.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of Smad2/3 and p38 MAP kinase in TGF-β1-induced epithelial-mesenchymal transition of pulmonary epithelial cells. AU - Kolosova,Irina, AU - Nethery,David, AU - Kern,Jeffrey A, PY - 2010/10/15/entrez PY - 2010/10/15/pubmed PY - 2011/4/16/medline SP - 1248 EP - 54 JF - Journal of cellular physiology JO - J Cell Physiol VL - 226 IS - 5 N2 - Idiopathic pulmonary fibrosis is characterized by myofibroblast accumulation, extracellular matrix (ECM) remodeling, and excessive collagen deposition. ECM-producing myofibroblasts may originate from epithelial cells through epithelial to mesenchymal transition (EMT). TGF-β1 is an inducer of EMT in pulmonary epithelial cells in vitro and in vivo, though the mechanisms are unclear. We hypothesized that TGF-β1 induced EMT through Smad-dependent and -independent processes. To test this hypothesis, we studied the roles and mechanisms of TGF-β1-induced Smad and p38 mitogen-activated protein kinase (MAPK) signaling in EMT-related changes in pulmonary epithelial cells. Exposure of pulmonary epithelial 1HAEo(-) cells to TGF-β1 resulted in morphological and molecular changes of EMT over a 96-h period; loss of cell-cell contact, cell elongation, down-regulation of E-cadherin, up-regulation of fibronectin, and up-regulation of collagen I. Both Smad2/3 and p38 MAPK signaling pathways were activated by TGF-β1. However, neither Smad2/3 nor p38 MAPK were required for the down-regulation of E-cadherin, yet p38 MAPK was associated with fibronectin up-regulation. Both Smad2/3 and p38 MAPK had a role in regulation of TGF-β1-induced collagen expression. Furthermore, these data demonstrate that Smads and p38 MAPK differentially regulate EMT-related changes in pulmonary epithelial cells. SN - 1097-4652 UR - https://www.unboundmedicine.com/medline/citation/20945383/Role_of_Smad2/3_and_p38_MAP_kinase_in_TGF_β1_induced_epithelial_mesenchymal_transition_of_pulmonary_epithelial_cells_ L2 - https://doi.org/10.1002/jcp.22448 DB - PRIME DP - Unbound Medicine ER -