title: SMAD7 antagonizes key TGFβ superfamily signaling in mouse granulosa cells in vitro.
abstract: Transforming growth factor β (TGFβ) superfamily signaling is essential for female reproduction. Dysregulation of the TGFβ signaling pathway can cause reproductive diseases. SMA and MAD (mothers against decapentaplegic) (SMAD) proteins are downstream signaling transducers of the TGFβ superfamily. SMAD7 is an inhibitory SMAD that regulates TGFβ signaling in vitro. However, the function of SMAD7 in the ovary remains poorly defined. To determine the signaling preference and potential role of SMAD7 in the ovary, we herein examined the expression, regulation, and function of SMAD7 in mouse granulosa cells. We showed that SMAD7 was expressed in granulosa cells and subject to regulation by intraovarian growth factors from the TGFβ superfamily. TGFB1 (TGFβ1), bone morphogenetic protein 4, and oocyte-derived growth differentiation factor 9 (GDF9) were capable of inducing Smad7 expression, suggesting a modulatory role of SMAD7 in a negative feedback loop. Using a small interfering RNA approach, we further demonstrated that SMAD7 was a negative regulator of TGFB1. Moreover, we revealed a link between SMAD7 and GDF9-mediated oocyte paracrine signaling, an essential component of oocyte-granulosa cell communication and folliculogenesis. Collectively, our results suggest that SMAD7 may function during follicular development via preferentially antagonizing and/or fine-tuning essential TGFβ superfamily signaling, which is involved in the regulation of oocyte-somatic cell interaction and granulosa cell function.
authors: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas 77843, USA.
authors: Yang
authors: Y
authors: Gao
authors: Haixia
authors: H
authors: Wen
authors: Chao
authors: C
authors: Wang
authors: Qinglei
authors: Q
authors: Li
mesh_terms: D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D006107:Granulosa Cells / Q000378:metabolism*; D055429:Growth Differentiation Factor 9 / Q000378:metabolism; D028322:Inhibin-beta Subunits / Q000378:metabolism; D051796:Inhibitor of Differentiation Proteins / Q000378:metabolism; D008024:Ligands; D051379:Mice; D009865:Oocytes / Q000378:metabolism; D019899:Paracrine Communication; D034741:RNA, Small Interfering; D015398:Signal Transduction; D051906:Smad7 Protein / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; C525898:Gdf9 protein, mouse; D055429:Growth Differentiation Factor 9; D051796:Inhibitor of Differentiation Proteins; D008024:Ligands; D034741:RNA, Small Interfering; D051906:Smad7 Protein; C497807:Smad7 protein, mouse; D016212:Transforming Growth Factor beta; D028322:Inhibin-beta Subunits