scholarly journals Regulation of ovarian function by the TGF-beta superfamily and follistatin

Reproduction ◽  
2003 ◽  
pp. 133-148 ◽  
Author(s):  
SY Lin ◽  
DJ Phillips ◽  
DM de Kretser ◽  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Ovarian Function ◽  
Tgf Beta ◽  
Morphogenetic Protein ◽  
Growth Differentiation Factor 9 ◽  
Growth Factor Beta ◽  
Potential Interactions

The role of follistatin as an activin-binding protein has dominated the study of this molecule for the last 10 years. However, there is emerging evidence that follistatin has a role in modulating the biology of other members of the transforming growth factor beta (TGF-beta) superfamily. This review summarizes the current concepts encompassing follistatin biochemistry as well as molecules with which it is functionally associated. Moreover, the importance of the two follistatin isoforms (follistatin-288 and follistatin-315) is discussed with particular emphasis on the regulation of the ovary. In addition to activin, this review discusses the functions of other members of the TGF-beta superfamily, for example growth differentiation factor 9 (GDF-9), bone morphogenetic protein 15 (BMP-15), BMP-6, BMP-4 and BMP-7, in the ovary, and the potential interactions between follistatin and these growth factors. The complex network of TGF-beta superfamily growth factor members involved in the modulation of ovarian function and the interactions of follistatin with these proteins is highlighted.

The emerging role of transforming growth factor-beta in kidney diseases

1994 ◽  
Vol 266 (6) ◽  
pp. F829-F842 ◽  
Author(s):  
K. Sharma ◽  
F. N. Ziyadeh
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Cellular Response ◽  
Transforming Growth Factor ◽  
The Body ◽  
Special Focus ◽  
Tgf Beta ◽  
Growth Factor Beta

Transforming growth factor-beta (TGF-beta) is a prototypical multifunctional cytokine, with growth being only one of its many functions. Its receptors and actions are germane to almost every cell in the body involved in tissue injury and repair, and its effects are best understood in the context of a cellular response to a changing environment. The broad areas in which TGF-beta plays a crucial role include cell proliferation and extracellular matrix production. TGF-beta is a key regulatory molecule in the control of the activity of fibroblasts and has been implicated in several disease states characterized by excessive fibrosis. In the kidney, TGF-beta promotes tubuloepithelial cell hypertrophy and regulates the glomerular production of almost every known molecule of the extracellular matrix, including collagens, fibronectin, tenascin, and proteoglycans, as well as the integrins that are the receptors for these molecules. Furthermore, TGF-beta blocks the destruction of newly synthesized extracellular matrix by upregulating the synthesis of protease inhibitors and downregulating the synthesis of matrix-degrading proteases such as stromelysin and collagenase. As will be discussed, there is a strong body of in vitro and in vivo evidence suggesting that persistent overproduction of TGF-beta 1 in glomeruli after the acute inflammatory stage of glomerulonephritis causes glomerulosclerosis. TGF-beta may also be important in a variety of other chronic renal disorders characterized by hypertrophy and sclerosis, such as diabetic nephropathy. In this review we will attempt to offer a basic understanding of the cellular and molecular biology of TGF-beta and its receptors, with special focus on the role of the TGF-beta system in the kidney during development, growth, and disease.

scholarly journals ALMS1 Regulates TGF-β Signaling and Morphology of Primary Cilia

2021 ◽  
Vol 9 ◽  
Author(s):  
María Álvarez-Satta ◽  
Mauro Lago-Docampo ◽  
Brais Bea-Mascato ◽  
Carlos Solarat ◽  
Sheila Castro-Sánchez ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Line ◽  
Transforming Growth Factor Beta ◽  
Primary Cilia ◽  
Transforming Growth Factor ◽  
Cellular Signaling ◽  
Bmp Signaling ◽  
Morphogenetic Protein ◽  
Growth Factor Beta

In this study, we aimed to evaluate the role of ALMS1 in the morphology of primary cilia and regulation of cellular signaling using a knockdown model of the hTERT-RPE1 cell line. ALMS1 depletion resulted in the formation of longer cilia, which often displayed altered morphology as evidenced by extensive twisting and bending of the axoneme. Transforming growth factor beta/bone morphogenetic protein (TGF-β/BMP) signaling, which is regulated by primary cilia, was similarly affected by ALMS1 depletion as judged by reduced levels of TGFβ-1-mediated activation of SMAD2/3. These results provide novel information on the role of ALMS1 in the function of primary cilia and processing of cellular signaling, which when aberrantly regulated may underlie Alström syndrome.

Experimental bilateral urinary obstruction in fetal sheep: transforming growth factor-beta 1 expression

1997 ◽  
Vol 273 (3) ◽  
pp. F372-F379 ◽  
Author(s):  
A. A. Medjebeur ◽  
L. Bussieres ◽  
B. Gasser ◽  
V. Gimonet ◽  
K. Laborde
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Urinary Obstruction ◽  
Urinary Concentration ◽  
Tgf Beta ◽  
Fetal Sheep ◽  
Type Iv ◽  
Growth Factor Beta

To gain insight into the role of transforming growth factor-beta 1 (TGF-beta 1) in the development of kidney pathology following fetal obstruction, we measured TGF-beta 1 gene expression, the active peptide, and the urinary concentration in a model of fetal bilateral urinary obstruction (BUO) in sheep. Fetal lambs underwent BUO at 60 (FO-60) or 80 days (FO-80) of gestation and were studied at 120 days. Independently of the onset or duration of obstruction, all fetuses developed type IV dysplasia (IV) associated with an arrest in the nephrogenesis or hydronephrosis. Fetal glomerular filtration rate was not significantly modified, whereas sodium tubular reabsorption was significantly decreased, and urinary TGF-beta 1 concentration was elevated in hydronephrosis but not in IV. Levels of TGF-beta 1 mRNA were increased in hydronephrosis compared with normal kidneys, and active TGF-beta 1 immunoreactivity was increased in both hydronephrotic and IV kidneys. In summary, TGF-beta 1 may play a role in the development of hydronephrosis and dysplasia in kidneys following fetal BUO. Its role in the arrest of nephrogenesis observed in the IV kidneys remains to be proved.

scholarly journals mRNA expression of type I and type II receptors for activin, transforming growth factor-beta, and bone morphogenetic protein in the murine erythroleukemic cell line, F5-5.fl

2000 ◽  
pp. 705-710 ◽  
Author(s):  
H Machida ◽  
K Ogawa ◽  
M Funaba ◽  
T Mizutani ◽  
M Tsujimoto
Keyword(s):  
Growth Factor ◽  
Mrna Expression ◽  
Bone Morphogenetic Protein ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Type I ◽  
Type Ii ◽  
Tgf Beta ◽  
Morphogenetic Protein ◽  
Growth Factor Beta

OBJECTIVE: Intracellular signaling of activin and transforming growth factor-beta (TGF-beta) is thought to be mediated by the same molecules (Smad2/3 and Smad4). Although differentiation of murine erythroleukemia F5-5.fl cells is induced by activin, it is not induced by TGF-beta, suggesting that at some point TGF-beta signaling is defective. The aim of this study was to investigate the unresponsiveness of F5-5.fl cells to TGF-beta. DESIGN: mRNA expression of ligands, receptors, and signal mediators for the TGF-beta family was examined in F5-5.fl cells using RT-PCR. RESULTS: Activin induced erythrodifferentiation of F5-5.fl cells in a dose-dependent manner. Neither TGF-beta1 nor bone morphogenetic protein (BMP)-4 affected the differentiation of F5-5.fl cells in the presence or absence of activin. Although mRNAs of TGF-betas (TGF-beta1, TGF-beta2 and TGF-beta3) were detected, those of inhibin/activin (alpha-, betaA- and betaB-subunits) and BMPs (BMP-2, BMP-4 and BMP-7) could not be detected in the cells, suggesting that neither activins nor BMPs are produced in F5-5.fl cells. The expression of both type I (ALK-4/ActRIB) and type II (ActRII) receptors for activin was detected in F5-5.fl cells. In contrast, while the expression of type I receptor for TGF-beta (ALK-5/TbetaRI) was detected, that of type II receptor (TbetaRII) was not. The mRNA of all Smads examined was detected in F5-5.fl cells. CONCLUSIONS: A defect in the type II receptor might cause unresponsiveness to TGF-beta in F5-5.fl cells. An erythrodifferentiation assay using F5-5.fl cells would be useful for measuring net activin activity because it would not be necessary to consider endogenous activins and BMPs.

scholarly journals Role of transforming growth factor-beta in the development of the mouse embryo.

1987 ◽  
Vol 105 (6) ◽  
pp. 2861-2876 ◽  
Author(s):  
U Heine ◽  
E F Munoz ◽  
K C Flanders ◽  
L R Ellingsworth ◽  
H Y Lam ◽  
...  
Keyword(s):  
Growth Factor ◽  
Mouse Embryo ◽  
Transforming Growth Factor Beta ◽  
Heart Valves ◽  
Transforming Growth Factor ◽  
Hair Follicles ◽  
Tgf Beta ◽  
Intense Staining ◽  
Growth Factor Beta

Using immunohistochemical methods, we have investigated the role of transforming growth factor-beta (TGF-beta) in the development of the mouse embryo. For detection of TGF-beta in 11-18-d-old embryos, we have used a polyclonal antibody specific for TGF-beta type 1 and the peroxidase-antiperoxidase technique. Staining of TGF-beta is closely associated with mesenchyme per se or with tissues derived from mesenchyme, such as connective tissue, cartilage, and bone. TGF-beta is conspicuous in tissues derived from neural crest mesenchyme, such as the palate, larynx, facial mesenchyme, nasal sinuses, meninges, and teeth. Staining of all of these tissues is greatest during periods of morphogenesis. In many instances, intense staining is seen in mesenchyme when critical interactions with adjacent epithelium occur, as in the development of hair follicles, teeth, and the submandibular gland. Marked staining is also seen when remodeling of mesenchyme or mesoderm occurs, as during formation of digits from limb buds, formation of the palate, and formation of the heart valves. The presence of TGF-beta is often coupled with pronounced angiogenic activity. The histochemical results are discussed in terms of the known biochemical actions of TGF-beta, especially its ability to control both synthesis and degradation of both structural and adhesion molecules of the extracellular matrix.

scholarly journals Identification of a novel transforming growth factor-beta (TGF-beta 5) mRNA in Xenopus laevis.

1990 ◽  
Vol 265 (2) ◽  
pp. 1089-1093 ◽  
Author(s):  
P Kondaiah ◽  
M J Sands ◽  
J M Smith ◽  
A Fields ◽  
A B Roberts ◽  
...  
Keyword(s):  
Growth Factor ◽  
Xenopus Laevis ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Tgf Beta ◽  
Growth Factor Beta

scholarly journals Recombinant type 1 transforming growth factor beta precursor produced in Chinese hamster ovary cells is glycosylated and phosphorylated.

1988 ◽  
Vol 8 (5) ◽  
pp. 2229-2232 ◽  
Author(s):  
A M Brunner ◽  
L E Gentry ◽  
J A Cooper ◽  
A F Purchio
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Chinese Hamster Ovary ◽  
Transforming Growth Factor ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Tgf Beta ◽  
Ovary Cells ◽  
Growth Factor Beta

Analyses of cDNA clones coding for simian type 1 transforming growth factor beta (TGF-beta 1) suggest that there are three potential sites for N-linked glycosylation located in the amino terminus of the precursor region. Analysis of [3H]glucosamine-labeled serum-free supernatants from a line of Chinese hamster ovary cells which secrete high levels of recombinant TGF-beta 1 indicate that the TGF-beta 1 precursor, but not the mature form, is glycosylated. Digestion with neuraminidase resulted in a shift in migration of the two TGF-beta 1 precursor bands, which suggests that they contain sialic acid residues. Endoglycosidase H had no noticeable effect. Treatment with N-glycanase produced two faster-migrating sharp bands, the largest of which had a molecular weight of 39 kilodaltons. TGF-beta 1-specific transcripts produced by SP6 polymerase programmed the synthesis of a 42-kilodalton polypeptide which, we suggest, is the unmodified protein backbone of the precursor. Labeling with 32Pi showed that the TGF-beta 1 precursor was phosphorylated in the amino portion of the molecule.

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