Tumor necrosis factor-alpha enhances both epithelial-mesenchymal transition and cell contraction induced in A549 human alveolar epithelial cells by transforming growth factor-beta1. 2010

Yasuhiro Yamauchi, and Tadashi Kohyama, and Hajime Takizawa, and Sumiko Kamitani, and Masashi Desaki, and Kazutaka Takami, and Shin Kawasaki, and Jun Kato, and Takahide Nagase
Department of Respiratory Medicine, The University of Tokyo, Tokyo, Japan. YAMAUCHIY-INT@h.u-tokyo.ac.jp

Recently, epithelial-mesenchymal transition (EMT) has been reported to contribute to tissue fibrosis through enhanced transforming growth factor (TGF)-beta1 signaling. Tumor necrosis factor (TNF)-alpha has also been implicated in tissue fibrosis. Therefore, the authors investigated whether TNF-alpha affected TGF-beta1-induced EMT. Cultured alveolar epithelial cells (A549 cells) were stimulated with TGF-beta1 (5 ng/mL), with/without TNF-alpha (10 ng/mL). TGF-beta1 induced EMT of A549 cells, with loss of E-cadherin and acquisition of vimentin. Combination of TNF-alpha with TGF-beta1 enhanced EMT, causing morphological changes, while quantitative polymerase chain reaction (PCR) showed suppression of E-cadherin mRNA and expression of vimentin mRNA. In addition, the gel contraction method revealed that cells that had undergone EMT acquired cell contractility, which is a feature of mesenchymal cells. Stimulation with TGF-beta1 induced cell contraction, as did TNF-alpha. Moreover, costimulation with TGF-beta1 and TNF-alpha enhanced the cell contraction. Although IFN-gamma suppressed spontaneous cell contraction, it did not suppress cell contraction, which was induced by TGF-beta1. In conclusion, TNF-alpha enhances not only EMT but also cell contraction induced by TGF-beta1. EMT might contribute to tissue fibrosis through induction of cell contraction.

UI MeSH Term Description Entries
D002282 Adenocarcinoma, Bronchiolo-Alveolar A carcinoma derived from epithelium of terminal bronchioles, in which the neoplastic tissue extends along the alveolar walls and grows in small masses within the alveoli. Involvement may be uniformly diffuse and massive, or nodular, or lobular. The neoplastic cells are cuboidal or columnar and form papillary structures. Mucin may be demonstrated in some of the cells and in the material in the alveoli, which also includes denuded cells. Metastases in regional lymph nodes, and in even more distant sites, are known to occur, but are infrequent. (From Stedman, 25th ed) Carcinoma, Alveolar,Carcinoma, Bronchiolar,Carcinoma, Bronchiolo-Alveolar,Adenocarcinoma, Alveolar,Alveolar Cell Carcinoma,Carcinoma, Bronchioloalveolar,Adenocarcinoma, Bronchiolo Alveolar,Adenocarcinomas, Alveolar,Adenocarcinomas, Bronchiolo-Alveolar,Alveolar Adenocarcinoma,Alveolar Adenocarcinomas,Alveolar Carcinoma,Alveolar Carcinomas,Alveolar Cell Carcinomas,Bronchiolar Carcinoma,Bronchiolar Carcinomas,Bronchiolo-Alveolar Adenocarcinoma,Bronchiolo-Alveolar Adenocarcinomas,Bronchiolo-Alveolar Carcinoma,Bronchiolo-Alveolar Carcinomas,Bronchioloalveolar Carcinoma,Bronchioloalveolar Carcinomas,Carcinoma, Alveolar Cell,Carcinoma, Bronchiolo Alveolar,Carcinomas, Alveolar,Carcinomas, Alveolar Cell,Carcinomas, Bronchiolar,Carcinomas, Bronchiolo-Alveolar,Carcinomas, Bronchioloalveolar
D004847 Epithelial Cells Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells. Adenomatous Epithelial Cells,Columnar Glandular Epithelial Cells,Cuboidal Glandular Epithelial Cells,Glandular Epithelial Cells,Squamous Cells,Squamous Epithelial Cells,Transitional Epithelial Cells,Adenomatous Epithelial Cell,Cell, Adenomatous Epithelial,Cell, Epithelial,Cell, Glandular Epithelial,Cell, Squamous,Cell, Squamous Epithelial,Cell, Transitional Epithelial,Cells, Adenomatous Epithelial,Cells, Epithelial,Cells, Glandular Epithelial,Cells, Squamous,Cells, Squamous Epithelial,Cells, Transitional Epithelial,Epithelial Cell,Epithelial Cell, Adenomatous,Epithelial Cell, Glandular,Epithelial Cell, Squamous,Epithelial Cell, Transitional,Epithelial Cells, Adenomatous,Epithelial Cells, Glandular,Epithelial Cells, Squamous,Epithelial Cells, Transitional,Glandular Epithelial Cell,Squamous Cell,Squamous Epithelial Cell,Transitional Epithelial Cell
D005355 Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Cirrhosis,Fibroses
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014409 Tumor Necrosis Factor-alpha Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS. Cachectin,TNF-alpha,Tumor Necrosis Factor Ligand Superfamily Member 2,Cachectin-Tumor Necrosis Factor,TNF Superfamily, Member 2,TNFalpha,Tumor Necrosis Factor,Cachectin Tumor Necrosis Factor,Tumor Necrosis Factor alpha
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D048430 Cell Shape The quality of surface form or outline of CELLS. Cell Shapes,Shape, Cell,Shapes, Cell
D053773 Transforming Growth Factor beta1 A subtype of transforming growth factor beta that is synthesized by a wide variety of cells. It is synthesized as a precursor molecule that is cleaved to form mature TGF-beta 1 and TGF-beta1 latency-associated peptide. The association of the cleavage products results in the formation a latent protein which must be activated to bind its receptor. Defects in the gene that encodes TGF-beta1 are the cause of CAMURATI-ENGELMANN SYNDROME. TGF-beta1,Transforming Growth Factor-beta1,TGF-beta-1,TGF-beta1 Latency-Associated Protein,TGF-beta1LAP,Transforming Growth Factor beta 1 Latency Associated Peptide,Transforming Growth Factor beta I,Latency-Associated Protein, TGF-beta1,TGF beta 1,TGF beta1 Latency Associated Protein,TGF beta1LAP
D054337 Cell Dedifferentiation A reverse developmental process in which terminally differentiated cells with specialized functions revert back to a less differentiated stage within their own CELL LINEAGE. Dedifferentiation, Cell,Cell Dedifferentiations,Dedifferentiations, Cell
D059630 Mesenchymal Stem Cells Mesenchymal stem cells, also referred to as multipotent stromal cells or mesenchymal stromal cells are multipotent, non-hematopoietic adult stem cells that are present in multiple tissues, including BONE MARROW; ADIPOSE TISSUE; and WHARTON JELLY. Mesenchymal stem cells can differentiate into mesodermal lineages, such as adipocytic, osteocytic and chondrocytic. Adipose Tissue-Derived Mesenchymal Stem Cell,Adipose Tissue-Derived Mesenchymal Stromal Cell,Adipose-Derived Mesenchymal Stem Cell,Bone Marrow Mesenchymal Stem Cell,Mesenchymal Stromal Cell,Mesenchymal Stromal Cells,Multipotent Bone Marrow Stromal Cell,Multipotent Mesenchymal Stromal Cell,Adipose Tissue-Derived Mesenchymal Stem Cells,Adipose Tissue-Derived Mesenchymal Stromal Cells,Adipose-Derived Mesenchymal Stem Cells,Adipose-Derived Mesenchymal Stromal Cells,Bone Marrow Mesenchymal Stem Cells,Bone Marrow Stromal Cell,Bone Marrow Stromal Cells,Bone Marrow Stromal Cells, Multipotent,Bone Marrow Stromal Stem Cells,Mesenchymal Progenitor Cell,Mesenchymal Progenitor Cells,Mesenchymal Stem Cell,Mesenchymal Stem Cells, Adipose-Derived,Mesenchymal Stromal Cells, Multipotent,Multipotent Bone Marrow Stromal Cells,Multipotent Mesenchymal Stromal Cells,Stem Cells, Mesenchymal,Wharton Jelly Cells,Wharton's Jelly Cells,Adipose Derived Mesenchymal Stem Cell,Adipose Derived Mesenchymal Stem Cells,Adipose Derived Mesenchymal Stromal Cells,Adipose Tissue Derived Mesenchymal Stem Cell,Adipose Tissue Derived Mesenchymal Stem Cells,Adipose Tissue Derived Mesenchymal Stromal Cell,Adipose Tissue Derived Mesenchymal Stromal Cells,Mesenchymal Stem Cells, Adipose Derived,Progenitor Cell, Mesenchymal,Progenitor Cells, Mesenchymal,Stem Cell, Mesenchymal,Stromal Cell, Mesenchymal,Stromal Cells, Mesenchymal,Wharton's Jelly Cell,Whartons Jelly Cells

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