Biomedical subjects

D Danielpour

Publications and source records attributed to D Danielpour.

At least 55 records · Page 3Linked to original sources

PubMed1991

Novel 150- and 180-kDa glycoproteins that bind transforming growth factor (TGF)-beta 1 but not TGF-beta 2 are present in several cell lines.

We identified transforming growth factor-beta (TGF-beta)-binding proteins which are distinct from previously described TGF-beta receptors or TGF-beta-binding proteins. These TGF-beta-binding proteins migrate as 150- and 180-kDa 125I-TGF-beta 1 affinity-labeled complexes which are consistently co-expressed in A549, Mv1Lu, MG-63, and BS-C-1 cells. They differ from the types I, II, and III TGF-beta receptors in their electrophoretic mobilities, their lack of binding to TGF-beta 2, and their failure to undergo the marked down-regulation seen with types I, II, and III receptors following a 16-h incubation with TGF-beta 1. The 150- and 180-kDa TGF-beta-binding proteins also are distinct from the recently described disulfide-linked TGF-beta 1-binding proteins which are present in rat glomeruli. In contrast to the glomerular TGF-beta 1-binding proteins, the electrophoretic mobilities of the 150- and 180-kDa binding proteins are unchanged following reduction. In addition, the 150- and 180-kDa TGF-beta-binding proteins are present in the detergent-rich phase during Triton X-114 phase separation, whereas the glomerular TGF-beta-binding proteins partition exclusively into the detergent-poor phase.

Affinity Labels↗

PubMed1991

Multiple forms of TGF-beta: distinct promoters and differential expression.

There are now five known distinct isoforms of TGF-beta with 64-82% identity. Of these, only TGF-beta 1, 2 and 3 thus far have been demonstrated to be expressed in mammalian tissues; TGF-beta 4 has been described only in chicken and TGF-beta 5 only in frog. Although the biological activities of these five isoforms of TGF-beta are indistinguishable in most in vitro assays their sites of synthesis and localization in vivo are often distinct. Expression of the various isoforms is differentially controlled both in vivo, as in development, and in vitro after treatment of cells with steroids, such as oestrogen or tamoxifen, or with retinoids. To investigate the basis of these observations we have cloned and characterized the promoters for the human TGF-beta 1, 2 and 3 genes. Significant differences have been found: whereas the TGF-beta 1 promoter has no TATAA box and is regulated principally by AP-1 sites, both the TGF-beta 2 and 3 promoters have TATAA boxes as well as AP-2 sites and cAMP-responsive elements. Accordingly, TGF-beta 1 gene expression is induced strongly by phorbol esters whereas that of TGF-beta 2 and 3 is induced by forskolin, an activator of adenylate cyclase. Expression of TGF-beta 2 and 3 is often coordinately regulated in vivo in a pattern distinct from that of TGF-beta 1.

Animals↗

PubMed1991

Cytokine induction in HTLV-I associated myelopathy and adult T-cell leukemia: alternate molecular mechanisms underlying retroviral pathogenesis.

The human T-cell lymphotropic virus type I (HTLV-I) is capable of inducing a variety of host cellular genes including many of the cytokines responsible for immune regulation and osteoclast activation. This derangement in cytokine expression may contribute to the panoply of disease states associated with HTLV-I infection such as the adult T-cell leukemia (ATL) and HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). We wished to determine if there was a correlation between the expression of an array of cytokines and the diverse clinical manifestations of ATL and HAM/TSP. Utilizing the techniques of specific mRNA amplification by the polymerase chain reaction (PCR) as well as Northern blotting, we analyzed the ex vivo mRNA expression of gamma-interferon (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and transforming growth factor-beta 1 (TGF-beta 1) in the peripheral blood of HAM/TSP and ATL patients as well as asymptomatic seropositive carriers. IFN-gamma, TNF-alpha, and IL-1 beta transcripts were up-regulated in patients with HAM/TSP and seropositive carriers when compared to their levels in ATL and normal controls. In contrast, the ATL patients constitutively expressed higher levels of TGF-beta 1 mRNA than HAM/TSP and seropositive carriers. In addition, TNF-alpha and IL-1 beta serum levels were elevated in HAM/TSP, but not in ATL patients nor seropositive carriers. However, the circulating leukemic cells from ATL patients secreted increased levels of TGF-beta 1 protein into the culture medium than T-cells derived from HAM/TSP patients. Collectively these results suggest that induction of IFN-gamma, TNF-alpha, and IL-1 beta in HAM/TSP may initiate an inflammatory cascade with subsequent events leading to immune mediated destruction of the central nervous system in these patients. Expression of osteoclast activators such as TNF-alpha and IL-1 beta is not associated with hypercalcemia in ATL. Finally, impaired cellular and humoral immune responses present in ATL, but not in HAM/TSP, may be related to elevated levels of TGF-beta 1 produced by the leukemic cells. These differences in retroviral-induced host cytokine expression in ATL and HAM/TSP suggest alternate roles in disease pathogenesis.

Adult↗

PubMed1991

Differential regulation of the expression of transforming growth factor-beta s 1 and 2 by retinoic acid, epidermal growth factor, and dexamethasone in NRK-49F and A549 cells.

Although most biological activities of transforming growth factor-beta s 1 and 2 (TGF-beta 1 and TGF-beta 2) examined in vitro are similar or identical, recent studies suggest that each of these factors may be independently regulated in vivo. In this study we have used highly sensitive and specific sandwich enzyme-linked immunosorbent assays for TGF-beta 1 and TGF-beta 2 to examine the effects of a variety of treatments on expression of these two TGF-beta isoforms. We show that epidermal growth factor (EGF) induces secretion of TGF-beta 1 and not TGF-beta 2, whereas retinoic acid (RA) induces secretion of TGF-beta 2 and not TGF-beta 1 in NRK-49F normal rat kidney fibroblasts and A549 human lung carcinoma cells. Moreover, treatment with EGF diminishes the levels of TGF-beta 2, while RA decreases the levels of TGF-beta 1 in both cell lines. Dexamethasone (Dex), on the other hand, inhibits the secretion of both TGF-beta 1 and TGF-beta 2 in A549 cells, while selectively inhibiting TGF-beta 1 secretion in NRK-49F cells. The interactive effects of EGF, RA, and Dex on the production of TGF-beta 1 and TGF-beta 2, which were studied on NRK-49F cells, demonstrate that EGF blocks the induction of TGF-beta 2 mRNA and peptide by RA, while Dex inhibits the induction of TGF-beta 1 mRNA and peptide by EGF. These results demonstrate that RA, EGF and Dex are each unique, differential, and interactive regulators of the expression of TGF-beta s 1 and 2.

Animals↗

PubMed1991

Localization of transforming growth factor-beta 1 in mitochondria of murine heart and liver.

Using both electron microscopic immunohistochemistry and cell fractionation techniques, we show that transforming growth factor-beta 1 (TGF-beta 1) is found in mitochondria of rat and mouse cardiac myocytes and rat hepatocytes. Four different polyclonal antibodies, raised against various epitopes encompassing the mature portion of the TGF-beta 1 molecule as well as the pro-region of its precursor, were used for the electron microscopy studies. The localization of TGF-beta 1 in mitochondria was confirmed by detection of the native peptide in mitochondria isolated from rat heart and liver; the majority of native TGF-beta 1 found in liver homogenates was recovered in highly pure mitochondrial fractions. The functional role of TGF-beta in the mitochondrion is unknown at present.

Animals↗

PubMed1991

Transforming growth factor-beta (TGF-beta) isoforms in rat liver regeneration: messenger RNA expression and activation of latent TGF-beta.

Expression of transforming growth factor-beta s (TGF-beta s) 1-3 was studied in normal liver and during liver regeneration after partial hepatectomy in the rat to determine whether each of these isoforms might be involved in hepatocyte growth in vivo. Expression of the mRNAs for all three TGF-beta isoforms increases in the regenerating liver. In addition, the levels of expression of the mRNAs for several extracellular matrix proteins, including fibronectin, vitronectin, laminin, and collagen, also increase in the regenerating liver. Immunohistochemical staining analysis shows a similar distribution of all three TGF-beta s in normal and regenerating liver; however, in both tissues, the level of expression of TGF-beta 1 is 8- to 10-fold higher than that of TGF-beta 2 as determined by sandwich enzyme-linked immunosorbent assay. Expression of all three TGF-beta mRNAs is restricted to liver nonparenchymal cells. Although hepatocytes from normal and regenerating livers do not synthesize TGF-beta, they are sensitive to inhibition of growth by all three TGF-beta isoforms. Hepatocytes from regenerating livers are capable of activating latent TGF-beta 1 complexes in vitro, whereas normal hepatocytes are not. The different TGF-beta isoforms may function in an inhibitory paracrine mechanism that is activated during liver regeneration and may also regulate the synthesis of extracellular matrix components in the regenerating liver.

Animals↗

PubMed1991

Hypoxia upregulates the synthesis of TGF-beta 1 by human dermal fibroblasts.

In this report, we have investigated the secretion and synthesis of transforming growth factor-beta 1 (TGF-beta 1) by human dermal fibroblast cultures in response to hypoxia (2% oxygen), and have compared it to standard oxygen culture conditions (15% oxygen at the cell surface). Sandwich enzyme-linked immunosorbent assay (SELISA) showed a selective and progressive increase in secretion of the TGF-beta 1 isoform in response to hypoxia, up to ninefold after cultures were exposed to low oxygen for 72 h; TGF-beta 2 peptide levels were not increased. We then investigated the transcriptional regulation of the TGF-beta 1 gene in response to low and standard oxygen tensions. In the first 24-48 h, TGF-beta 1 mRNA levels decreased steadily in both oxygen environments. This mRNA decline continued for up to 72 h in standard oxygen but not in cultures exposed to low oxygen tension. At 72 h, steady-state TGF-beta 1 mRNA levels were 8 times greater in low compared to standard oxygen, and this increase was reversible upon re-exposure of fibroblast cultures to standard oxygen tension for 24 h. Elevated TGF-beta 1 m-RNA levels in both low and standard oxygen declined steadily and with the same half-life after the addition of actinomycin D, suggesting that hypoxia increased TGF-beta 1 transcription rather than mRNA stability. We conclude that low oxygen tension upregulates the synthesis of TGF-beta 1 by human dermal fibroblasts, and leads to increased secretion of this peptide.

Cell Hypoxia↗

PubMed1991

Overexpression of transforming growth factor-beta in transgenic mice carrying the human T-cell lymphotropic virus type I tax gene.

Human T-cell lymphotropic virus type I (HTLV-I) has been associated with an adult form of T-cell leukemia as well as tropical spastic paraparesis, a neurodegenerative disease. Adult T-cell leukemia patients express high levels of the type 1 isoform of transforming growth factor-beta (TGF-beta 1), which is mediated by the effects of the HTLV-I Tax transactivator protein on the TGF-beta 1 promoter. To understand further the regulation of TGF-beta 1 expression by Tax, we examined its expression in transgenic mice carrying the HTLV-I tax gene. We show that tumors from these mice and other tissues, such as submaxillary glands and skeletal muscle, which express high levels of tax mRNA selectively express high levels of TGF-beta 1 mRNA and protein. Moreover, TGF-beta 1 significantly stimulated the incorporation of tritiated thymidine into one of three cell lines derived from neurofibromas of tax-transgenic mice, which suggests that the excessive production of TGF-beta 1 may play a role in tumorigenesis and that these mice may serve as a useful model for studying the biological effects of TGF-beta in vivo.

Animals↗

PubMed1991

The growth inhibition of human breast cancer cells by a novel synthetic progestin involves the induction of transforming growth factor beta.

Recent experimental work has identified a novel intracellular binding site for the synthetic progestin, Gestodene, that appears to be uniquely expressed in human breast cancer cells. Gestodene is shown here to inhibit the growth of human breast cancer cells in a dose-dependent fashion, but has no effect on endocrine-responsive human endometrial cancer cells. Gestodene induced a 90-fold increase in the secretion of transforming growth factor-beta (TGF-beta) by T47D human breast cancer cells. Other synthetic progestins had no effect, indicating that this induction is mediated by the novel Gestodene binding site and not by the conventional progesterone receptor. Furthermore, in four breast cancer cell lines, the extent of induction of TGF-beta correlated with intracellular levels of Gestodene binding site. No induction of TGF-beta was observed with the endometrial cancer line, HECl-B, which lacks the Gestodene binding site, but which expresses high levels of progesterone receptor. The inhibition of growth of T47D cells by Gestodene is partly reversible by a polyclonal antiserum to TGF-beta. These data indicate that the growth-inhibitory action of Gestodene may be mediated in part by an autocrine induction of TGF-beta.

Binding Sites↗

PubMed1991

Rat thecal/interstitial cells express transforming growth factor-beta type 1 and 2, but only type 2 is regulated by gonadotropin in vitro.

We previously demonstrated that granulosa cells from diethylstilbestrol-primed immature rats expressed transforming growth factor-beta 2 (TGF beta 2), but not TGF beta 1, mRNA and that its expression was regulated by FSH in vitro. The present studies were designed, therefore, to establish whether thecal/interstitial cells (TIC) from diethylstilbestrol-primed immature rats express more than one subtype of TGF beta mRNA and gene product and whether the levels of expression/production in vitro were regulated by LH/hCG. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of total RNA indicated that TIC expressed both TGF beta 1 and TGF beta 2 mRNA. In response to hCG (200 ng/ml), TIC expressed TGF beta 2 mRNA levels that were 51% of control levels; TGF beta 1 mRNA levels were not altered. In response to cholera toxin (10(-9) M), TIC expression of TGF beta 2 and TGF beta 1 mRNA levels was 10% and 55% of control values, respectively. Western blot analysis established that both TGF beta 1 and TGF beta 2 were secreted in vitro. hCG and cholera toxin reduced secretion of TGF beta bioactivity by 55% and 90%, respectively. In summary, these results indicate: 1) TIC express both TGF beta 1 and TGF beta 2 mRNA; 2) TIC expression of TGF beta 2, but not TGF beta 1, mRNA is regulated by hCG in vitro; 3) TIC secrete both TGF beta 1 and TGF beta 2, and 4) TIC secretion in vitro of TGF beta activity is gonadotropin regulated.

Animals↗

PubMed1991

Identification of transforming growth factor-beta as an immunosuppressive factor in aqueous humor.

The anterior chamber of the eye is an immunologically privileged site. Over the past 15 years, numerous laboratories documented that the privileged status of this unique site is mediated by multifactorial immunoregulatory processes. Among the participating factors is the aqueous humor that circulates in the anterior chamber and is in contact with most of the tissues in the anterior segment of the eye. Recently, it was found that normal aqueous humor is a powerful inhibitor of antigen-driven T lymphocyte activation, but it spares other important functional properties of T cells. The spectrum of immune inhibitory properties resembles some of the activities of transforming growth factor-beta (TGF-beta), a polypeptide cytokine. Because of this similarity, the authors tried to determine if TGF-beta is present in aqueous humor and whether this cytokine could account for the lymphocyte inhibitory activity of this biologic fluid. They found TGF-beta in aqueous humor by dot-blot analysis. Using the CCL-64 mink lung epithelial cell bioassay for this compound, TGF-beta bioactivity was shown in aqueous humor from several different species, including human. In rabbit and human aqueous humor, most of the biologic activity was due to TGF-beta 2 (80-90%). Dose-response curves generated by using purified porcine TGF-beta showed that aqueous humor contained sufficient concentrations of TGF-beta to account for the observed inhibition in several assays for T cell activation and proliferation. Partial purification of the lymphocyte inhibitor in rabbit aqueous humor by size exclusion in high-performance liquid chromatography demonstrated that several lymphocyte inhibitory fractions contained TGF-beta bioactivity. Finally, neutralizing antisera to TGF-beta 2 were able to reverse most of the lymphocyte inhibitory activity of aqueous humor. It was concluded that TGF-beta was present in high concentration in normal aqueous humor and that this cytokine contributed to the immunosuppressive properties of aqueous humor.

Animals↗

PubMed1990

Transactivation of the transforming growth factor beta 1 (TGF-beta 1) gene by human T lymphotropic virus type 1 tax: a potential mechanism for the increased production of TGF-beta 1 in adult T cell leukemia.

We examined the effect of the human T lymphotropic virus type 1 (HTLV-I) Tax gene product on the human transforming growth factor beta 1 (TGF-beta 1) promoter. Transfection of deleted constructs of the TGF-beta 1 promoter revealed regions homologous with AP-1 binding sites that were required for Tax-induced transactivation of the TGF-beta 1 promoter. In addition, we examined the expression and secretion of TGF-beta in fresh leukemic cells isolated from patients with adult T cell leukemia (ATL) and in HTLV-1-infected T cell lines. We report that fresh leukemic cells from ATL patients constitutively produce high levels of TGF-beta 1 mRNA and secrete TGF-beta 1 but not TGF-beta 2 into the culture medium. In addition, long-term ATL cell lines expressed significant amounts of TGF-beta 1 mRNA as well as detectable levels of TGF-beta 1 protein. These results suggest a role for Tax in the upregulation of TGF-beta 1 in HTLV-I-infected cells.

Cell Line↗

PubMed1990

Identification of disulfide-linked transforming growth factor-beta 1-specific binding proteins in rat glomeruli.

We have identified two distinct classes of transforming growth factor-beta (TGF-beta)-binding proteins by affinity labeling rat glomeruli with 125I-TGF-beta 1 and 125I-TGF-beta 2. The first type consists of a group of proteins that bind TGF-beta 1 but do not bind TGF-beta 2. When 125I-TGF-beta 1 affinity-labeled glomeruli were separated under nonreducing conditions, four prominent bands with Mr values of 320,000, 260,000, 170,000, and 90,000 were observed. Following reduction, the 320,000 and 170,000 bands yielded only a 100,000 band, the 260,000 complex yielded bands of 200,000, 100,000, and 85,000, and the 90,000 band migrated with an Mr of 85,000. Binding of 125I-TGF-beta 1 to these proteins was unaffected by the addition of as much as a 1,000-fold excess of TGF-beta 2. The second type of glomerular TGF-beta-binding protein consists of Mr 160,000-200,000 and 280,000 proteins that bind both TGF-beta 1 and beta 2. Digestion of these affinity-labeled proteins with heparitinase and chondroitinase resulted in a decrease of approximately 40,000 in their apparent molecular weights. Glomerular TGF-beta 1-binding proteins are distinct from previously described TGF-beta-binding proteins in their specificity for TGF-beta 1 and their formation of disulfide-linked multimers. The TGF-beta 1/beta 2-binding proteins share some properties of the previously described type III TGF-beta receptor.

Affinity Labels↗

PubMed1990

Differential inhibition of transforming growth factor beta 1 and beta 2 activity by alpha 2-macroglobulin.

Affinity labeling and immunoprecipitation studies demonstrate that alpha 2-macroglobulin (alpha 2M) is the major serum-binding protein for transforming growth factors beta 1 and beta 2 (TGF-beta 1 and TGF-beta 2). Purified alpha 2M inhibits the binding of both 125I-TGF-beta 1 and 125I-TGF-beta 2 to cell surface receptors at I50 values of 200 and 10 micrograms/ml, respectively. alpha 2M (200 micrograms/ml) does not block TGF-beta 1 inhibition of CCL-64 mink lung cell growth but reduces this activity of TGF-beta 2 10-fold. The electrophoretic migration of 125I-TGF-beta.alpha 2M complexes on polyacrylamide gels under nondenaturing conditions demonstrates that alpha 2M has 10-fold greater affinity for TGF-beta 2 than for TGF-beta 1. Each of these complexes comigrates as a single band with the fast form of alpha 2M. We suggest that alpha 2M is an important differential regulator of the biological activities of TGF-beta 1 and TGF-beta 2 in vivo.

Animals↗

PubMed1990

Anti-oestrogens induce the secretion of active transforming growth factor beta from human fetal fibroblasts.

The clinical use of anti-oestrogens in breast cancer therapy has traditionally been restricted to tumours that contain measurable oestrogen receptor protein. However, it is now widely recognised that the clinical response to adjuvant anti-oestrogen therapy appears to be independent of the oestrogen receptor content of the primary tumour. The study reported here was designed to investigate the possibility that human stromal cells can respond to anti-oestrogens by an increased synthesis of the inhibitory growth factor, transforming growth factor beta (TGF-beta). Two established human fetal fibroblast strains were used as models for the breast cancer stromal fibroblasts. These cells were found to respond to the addition of anti-oestrogens by a large increase in their synthesis of biologically active TGF-beta. Despite the application of ligand binding, immunoassay and Northern analysis, no oestrogen receptor or oestrogen receptor mRNA was detected in either of the human fetal fibroblasts strains. These observations may provide a mechanism of action of anti-oestrogens that is independent of the presence of oestrogen receptor in the tumour epithelial cells, and thus provide an explantation for the counter-intuitive results of adjuvant anti-oestrogen action.

Blotting, Northern↗

PubMed1990

Expression of transforming growth factor-beta 1 and beta 2 in rat glomeruli.

The transforming growth factors-beta are potent modulators of cell growth and extracellular matrix metabolism in most types of cultured cells. The distribution and functions of TGF-beta in vivo are less well known. We utilized several different techniques including northern blots, a CCl-64 cell growth inhibition assay, and sandwich enzyme-linked immunosorbent assays (SELISA) to examine the expression of TGF-beta 1 and TGF-beta 2 in rat glomeruli. High levels of TGF-beta 1 mRNA and protein were found in glomeruli (56 +/- 22 ng TGF-beta 1/g tissue). These levels were several-fold higher than those present in whole kidney (10 +/- 5 ng/g). TGF-beta 2 mRNA was present in glomeruli but was not detected in whole kidney. TGF-beta 2 concentrations by SELISA were 19 +/- 8 ng TGF-beta 2/g in glomeruli and less than 5 ng/g in whole kidney. Since TGF-beta has such marked effects on cell growth, we also examined whether alterations in TGF-beta expression were associated with the renal hypertrophy which follows unilateral nephrectomy. Expression of TGF-beta 1 mRNA decreased in glomeruli following nephrectomy. However, this was not associated with a significant fall in glomerular TGF-beta 1 protein concentration. Whole kidney levels of TGF-beta 1 and its mRNA were unchanged following nephrectomy. Similar results were obtained for TGF-beta 2. Our data document the presence of high concentrations of TGF-beta 1 and beta 2 and their corresponding mRNAs in normal rat glomeruli. These results suggest that TGF-beta may play important regulatory roles in the normal glomerulus.

Animals↗

PubMed1990

Induction and autocrine receptor binding of transforming growth factor-beta 2 during terminal differentiation of primary mouse keratinocytes.

Primary cultures of mouse keratinocytes maintain a basal cell phenotype in 0.05 mM Ca2+ medium, while culture in 1.4 mM Ca2+ results in terminal differentiation and inhibition of DNA synthesis. Induction of differentiation by Ca2+ results in a 10- to 20-fold increase in the expression of transforming growth factor-beta 2 (TGF-beta 2) mRNA and peptide, but a decrease in the expression of TGF-beta 1. In contrast, binding and cross-linking analyses show that the number of available surface 80 kilodalton (kDa) and 65 kDa TGF-beta receptor types decrease during differentiation. However, a mild acid wash significantly increases the number of available receptor sites on the differentiated keratinocytes, indicating that the TGF-beta receptors are unavailable for binding due to masking by endogenous ligand. A significant level of TGF-beta 2 secretion and receptor binding occur before the decrease in DNA synthesis, suggesting that the inhibition of DNA synthesis associated with differentiation of keratinocytes is mediated through the production and autocrine action of TGF-beta 2.

Animals↗

PubMed1990

Mesoderm induction in Xenopus laevis distinguishes between the various TGF-beta isoforms.

Induction of mesoderm in ectodermal explants of Xenopus laevis blastula embryos had previously been shown to respond selectively to TGF-beta 2, with TGF-beta s 1 and 5 having no activity in this assay. As TGF-beta s 1, 2, and 3 are frequently coexpressed in tissues, we wished to examine the activity of TGF-beta 3 relative to that of TGF-beta s 1 and 2 in this assay as well as in other in vitro assays. We report here that when the activity of recombinant TGF-beta 3 is normalized to that of TGF-beta 1 in the assay for growth inhibition in CCL-64 cells, it is also equal to that of TGF-beta 1 in assays for stimulation of both anchorage-independent growth of rat NRK cells and chemotaxis of human monocytes. In contrast, in the assay for mesoderm induction, recombinant TGF-beta 3 is 10-fold more active than TGF-beta 2, inducing expression of muscle specific alpha-actin at concentrations as low as 1 ng/ml. These results suggest that more complex systems, in contrast to individual cell types, may respond selectively to the various TGF-beta isoforms and that there might be biological consequences of TGF-beta isoform switching in vivo.

Animals↗