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Transforming growth factor β signaling in uterine development and function.

Li Q - J Anim Sci Biotechnol (2014)

Bottom Line: Mounting evidence supports its important role in female reproduction and development.By drawing on mouse and human studies as a main source, this review focuses on the recent progress on understanding TGFβ signaling in the uterus.The review also considers the involvement of dysregulated TGFβ signaling in pathological conditions that cause pregnancy loss and fertility problems in women.

View Article: PubMed Central - PubMed

Affiliation: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843 USA.

ABSTRACT
Transforming growth factor β (TGFβ) superfamily is evolutionarily conserved and plays fundamental roles in cell growth and differentiation. Mounting evidence supports its important role in female reproduction and development. TGFBs1-3 are founding members of this growth factor family, however, the in vivo function of TGFβ signaling in the uterus remains poorly defined. By drawing on mouse and human studies as a main source, this review focuses on the recent progress on understanding TGFβ signaling in the uterus. The review also considers the involvement of dysregulated TGFβ signaling in pathological conditions that cause pregnancy loss and fertility problems in women.

No MeSH data available.


Related in: MedlinePlus

Canonical and non-canonical TGFβ signaling. In the canonical pathway, TGFβ ligands bind to serine/threonine kinase type II and type I receptors and phosphorylate R-SMADs, which form heteromeric complexes with SMAD4 and translocate into the nucleus to regulate gene transcription. The non-canonical pathway generally refers to the SMAD-independent pathway such as PI3K-AKT, ERK1/2, p38, and JNK pathways. Recent studies have identified an “R-SMAD-dependent but SMAD4-independent” non-canonical pathway that regulates miRNA maturation.
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Fig1: Canonical and non-canonical TGFβ signaling. In the canonical pathway, TGFβ ligands bind to serine/threonine kinase type II and type I receptors and phosphorylate R-SMADs, which form heteromeric complexes with SMAD4 and translocate into the nucleus to regulate gene transcription. The non-canonical pathway generally refers to the SMAD-independent pathway such as PI3K-AKT, ERK1/2, p38, and JNK pathways. Recent studies have identified an “R-SMAD-dependent but SMAD4-independent” non-canonical pathway that regulates miRNA maturation.

Mentions: TGFβ signals through both SMAD-dependent (i.e., canonical) and SMAD-independent (i.e., non-canonical) pathways in a contextually dependent manner [2, 8, 14–16] (Figure 1). The non-canonical pathways serve to integrate signaling from other signaling cascades, resulting in a quantitative output in a given context. Davis and colleagues [17] have recently suggested the presence of microRNA (miRNA)-mediated non-canonical pathway, where TGFβ signaling promotes the biosynthesis of a subset of miRNAs via interactions between R-SMADs and a consensus RNA sequence of miRNAs within the DROSHA (drosha, ribonuclease type III) complex [17–19]. Thus, this type of non-canonical signaling requires R-SMADs but not SMAD4. Multiple regulatory layers including ligand traps (e.g., follistatin), inhibitory SMADs, and interactive pathways exist to determine the signaling output and precisely control TGFβ signaling activity [4, 8, 20–23]. For instance, the linker region of R-SMADs is subject to the phosphorylation modification by mitogen-activated protein kinases (MAPKs) [24]. Therefore, the variable responses triggered by this growth factor superfamily and the complex signaling circuitries within a given cell population underscore the importance of a fine-tuned TGFβ signaling system at both the cellular and systemic levels.Figure 1


Transforming growth factor β signaling in uterine development and function.

Li Q - J Anim Sci Biotechnol (2014)

Canonical and non-canonical TGFβ signaling. In the canonical pathway, TGFβ ligands bind to serine/threonine kinase type II and type I receptors and phosphorylate R-SMADs, which form heteromeric complexes with SMAD4 and translocate into the nucleus to regulate gene transcription. The non-canonical pathway generally refers to the SMAD-independent pathway such as PI3K-AKT, ERK1/2, p38, and JNK pathways. Recent studies have identified an “R-SMAD-dependent but SMAD4-independent” non-canonical pathway that regulates miRNA maturation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4255921&req=5

Fig1: Canonical and non-canonical TGFβ signaling. In the canonical pathway, TGFβ ligands bind to serine/threonine kinase type II and type I receptors and phosphorylate R-SMADs, which form heteromeric complexes with SMAD4 and translocate into the nucleus to regulate gene transcription. The non-canonical pathway generally refers to the SMAD-independent pathway such as PI3K-AKT, ERK1/2, p38, and JNK pathways. Recent studies have identified an “R-SMAD-dependent but SMAD4-independent” non-canonical pathway that regulates miRNA maturation.
Mentions: TGFβ signals through both SMAD-dependent (i.e., canonical) and SMAD-independent (i.e., non-canonical) pathways in a contextually dependent manner [2, 8, 14–16] (Figure 1). The non-canonical pathways serve to integrate signaling from other signaling cascades, resulting in a quantitative output in a given context. Davis and colleagues [17] have recently suggested the presence of microRNA (miRNA)-mediated non-canonical pathway, where TGFβ signaling promotes the biosynthesis of a subset of miRNAs via interactions between R-SMADs and a consensus RNA sequence of miRNAs within the DROSHA (drosha, ribonuclease type III) complex [17–19]. Thus, this type of non-canonical signaling requires R-SMADs but not SMAD4. Multiple regulatory layers including ligand traps (e.g., follistatin), inhibitory SMADs, and interactive pathways exist to determine the signaling output and precisely control TGFβ signaling activity [4, 8, 20–23]. For instance, the linker region of R-SMADs is subject to the phosphorylation modification by mitogen-activated protein kinases (MAPKs) [24]. Therefore, the variable responses triggered by this growth factor superfamily and the complex signaling circuitries within a given cell population underscore the importance of a fine-tuned TGFβ signaling system at both the cellular and systemic levels.Figure 1

Bottom Line: Mounting evidence supports its important role in female reproduction and development.By drawing on mouse and human studies as a main source, this review focuses on the recent progress on understanding TGFβ signaling in the uterus.The review also considers the involvement of dysregulated TGFβ signaling in pathological conditions that cause pregnancy loss and fertility problems in women.

View Article: PubMed Central - PubMed

Affiliation: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843 USA.

ABSTRACT
Transforming growth factor β (TGFβ) superfamily is evolutionarily conserved and plays fundamental roles in cell growth and differentiation. Mounting evidence supports its important role in female reproduction and development. TGFBs1-3 are founding members of this growth factor family, however, the in vivo function of TGFβ signaling in the uterus remains poorly defined. By drawing on mouse and human studies as a main source, this review focuses on the recent progress on understanding TGFβ signaling in the uterus. The review also considers the involvement of dysregulated TGFβ signaling in pathological conditions that cause pregnancy loss and fertility problems in women.

No MeSH data available.


Related in: MedlinePlus