title: The expression of Smads and transforming growth factor beta receptors in leiomyoma and myometrium and the effect of gonadotropin releasing hormone analogue therapy.
abstract: Gene microarray analysis indicated that several components of the transforming growth factor beta receptor (TGF-betaR) signaling pathway are differentially expressed in leiomyoma and myometrium. To validate the microarray results we evaluated the expression of Smads, intracellular proteins that transmit TGF-betaR signals, in leiomyoma and matched myometrium from untreated women, and women who received gonadotropin releasing hormone analogue (GnRHa) therapy. Semi-quantitative RT-PCR, Western blotting and immunohistochemistry indicate that leiomyoma and myometrium expresses receptor-activated Smad3, common Smad4 and inhibitory Smad7, with elevated expression of Smad3, Smad4 and phosphorylated Smad3 (pSmad3) as well as TGF-betaR type I and type II in leiomyoma compared to myometrium (P<0.05). GnRHa therapy resulted in lowering of TGF-betaRs as well as Smad4 and pSmad3, with concurrent increased in Smad7 expression in both leiomyoma and myometrium compared to untreated group (P<0.05). Immunohistochemically Smads and pSmad3 were localized in cytoplasmic/nuclear compartments of leiomyoma and myometrial smooth muscle cells and connective tissue fibroblasts, with alteration in their intensity (HScores) in GnRHa-treated group. In conclusion, the results indicates that leiomyoma and myometrium express all the components of TGF-betaR and Smads, and GnRHa therapy results in alteration of their expression further supporting the importance of TGF-beta system as key regulator of leiomyoma growth.
authors: Department of OB/GYN, University of Florida, Gainesville, FL 32610, USA. cheginin@obgyn.ufl.edu
authors: Nasser
authors: N
authors: Chegini
authors: Xiaoping
authors: X
authors: Luo
authors: Li
authors: L
authors: Ding
authors: Daylene
authors: D
authors: Ripley
mesh_terms: D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007889:Leiomyoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D016729:Leuprolide / Q000627:therapeutic use*; D009215:Myometrium / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis / Q000378:metabolism*; D051900:Smad3 Protein; D051901:Smad4 Protein; D051906:Smad7 Protein; D015534:Trans-Activators / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; C497790:SMAD3 protein, human; C497796:SMAD4 protein, human; C497806:SMAD7 protein, human; D051900:Smad3 Protein; D051901:Smad4 Protein; D051906:Smad7 Protein; D015534:Trans-Activators; D016729:Leuprolide