Involvement of KLF14 and egr-1 in the TGF-beta1 action on Leydig cell proliferation

► TGF-1 in the presence of progesterone induces Leydig cell proliferation. ► Progesterone abolished p15 gene expression induced by TGF-1 in Leydig cells. ► KLF-14 and egr-1 is involved in the signaling pathway of TGF-1 on Leydig cell proliferation. Transforming growth factor β1 (TGF-β1) is a pleiotr...

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Published in:	Cytokine (Philadelphia, Pa.) Vol. 61; no. 2; pp. 670 - 675
Main Authors:	Gonzalez, C.R., Vallcaneras, S.S., Calandra, R.S., Gonzalez Calvar, S.I.
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 01-02-2013
Subjects:	Activin Receptors, Type I - genetics Activin Receptors, Type I - metabolism Animals cell cycle Cell Line cell proliferation Cell Proliferation - drug effects culture media cultured cells Cyclin-Dependent Kinase Inhibitor p15 - metabolism Cytokines DNA, Complementary - genetics Early Growth Response Protein 1 - metabolism EGR-1 protein Endoglin gene expression Gene Expression Regulation - drug effects genes Homeostasis Humans Intracellular Signaling Peptides and Proteins - genetics Intracellular Signaling Peptides and Proteins - metabolism KLF14 Kruppel-Like Transcription Factors - metabolism Leydig cells Leydig Cells - cytology Leydig Cells - drug effects Leydig Cells - metabolism Male Media (culture) Mice Mice, Inbred BALB C Progesterone Progesterone - pharmacology Progesterone receptors Proliferating Cell Nuclear Antigen - metabolism Proliferation Protein-Serine-Threonine Kinases - genetics Protein-Serine-Threonine Kinases - metabolism Real-Time Polymerase Chain Reaction Receptors, Transforming Growth Factor beta - genetics Receptors, Transforming Growth Factor beta - metabolism Response Elements - genetics Signal transduction TGF-β1 Transcription Factors - metabolism transforming growth factor beta 1 Transforming Growth Factor beta1 - genetics Transforming Growth Factor beta1 - metabolism Transforming Growth Factor beta1 - pharmacology Transforming growth factor- beta TGF-β1 Proliferation KLF14 Leydig cells
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Summary:	► TGF-1 in the presence of progesterone induces Leydig cell proliferation. ► Progesterone abolished p15 gene expression induced by TGF-1 in Leydig cells. ► KLF-14 and egr-1 is involved in the signaling pathway of TGF-1 on Leydig cell proliferation. Transforming growth factor β1 (TGF-β1) is a pleiotropic cytokine that modulates cell homeostasis. In Leydig cells, TGF-β1 exerts stimulatory and inhibitory effect depending on the type I receptor involved in the signaling pathway. The aim of the present work was to study the signaling mechanisms and the intermediates involved in the action of TGF-β1 on TM3 Leydig cell proliferation in the presence or absence of progesterone. The MTT assay showed that the presence of progesterone in the culture media lead to a proliferative effect that was blocked by Ru 486, an inhibitor of progesterone receptor; and ALK-5 did not participate in this effect. TGF-β1 (1ng/ml) increased the expression of p15 (an inhibitor of cell cycle) in TM3 Leydig cells, and this effect was blocked by progesterone (1μM). The expression of PCNA presented a higher increase in the cell cultured with TGF-β1 plus progesterone than in cells cultured only with TGF-β1. Progesterone induced the gene expression of endoglin, a cofactor of TGF-β1 receptor that leads to a stimulatory signaling pathway, despite of the absence of progesterone response element in endoglin gene. In addition, the presence of progesterone induced the gene expression of egr-1 and also KLF14, indicating that this steroid channels the signaling pathway into a non-canonical mechanism. In conclusion, these findings suggest that the proliferative action of TGF-β1 involves endoglin. This co-receptor might be induced by KLF14 which is probably activated by progesterone.
Bibliography:	http://dx.doi.org/10.1016/j.cyto.2012.12.009 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	1043-4666 1096-0023
DOI:	10.1016/j.cyto.2012.12.009