Metanephric transforming growth factor-beta 1 regulates nephrogenesis in vitro

1993 ◽  
Vol 264 (6) ◽  
pp. F996-F1002 ◽  
Author(s):  
S. A. Rogers ◽  
G. Ryan ◽  
A. F. Purchio ◽  
M. R. Hammerman
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Tgf Beta ◽  
Rat Embryos ◽  
Igf I ◽  
Metanephric Blastema

Development of the metanephric kidney during embryogenesis is regulated by a number of polypeptide growth factors of renal origin. We have defined previously a role for insulin-like growth factors (IGF) I and II and for transforming growth factor (TGF)-alpha. To delineate the effect of TGF-beta 1, on renal organogenesis, we cultured metanephroi surgically dissected from 13-day-old rat embryos in serum-free chemically defined media. TGF-beta 1 mRNA was present in kidneys from 13-day-old rat embryos, and positive immunostaining for TGF-beta 1 could be demonstrated in cultured metanephroi. However, TGF-beta bioactivity could not be detected in media obtained from the metanephroi. Addition of 10(-9) M TGF-beta 1 to cultures inhibited tubulogenesis, but had no effect on synthesis of IGF-I or -II. Addition of anti-TGF-beta 1 antibodies to cultures accelerated tubulogenesis within the metanephric blastema. These findings establish the potential for TGF-beta 1 production within the rat metanephros during development in vivo. It is possible that this peptide exerts a negative control on the process of tubulogenesis within metanephric blastema and in this manner acts to shape the architecture of mature kidney.

Modulation of growth factor incorporation into ECM of human osteoblast-like cells in vitro by 17 beta-estradiol

1994 ◽  
Vol 267 (6) ◽  
pp. E990-E1001 ◽  
Author(s):  
M. Slater ◽  
J. Patava ◽  
K. Kingham ◽  
R. S. Mason
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Bone Growth ◽  
Transforming Growth Factor ◽  
Bone Matrix ◽  
Tgf Beta ◽  
Subsequent Formation ◽  
Igf I

Human fetal osteoblast-like cells formed a regular multilayered structure in vitro with an extensive collagen-based extracellular matrix. With colloidal gold immunocytochemistry, labels for alkaline phosphatase and osteocalcin were distributed in a relatively diffuse pattern, in contrast to the bone growth factors, insulin-like growth factors I and II (IGF-I and IGF-II), transforming growth factor-beta 1 (TGF-beta 1), and basic fibroblast growth factor, which were colocalized in the collagenous matrix of the multilayer. The inclusion of 17 beta-estradiol (10(-11) to 10(-9) M) in the culture medium increased multilayer depths, increased labeling for IGF-I, IGF-II, and TGF-beta 1, and resulted in earlier detection of TGF-beta 1 label. In contrast, the increase in multilayer depth resulting from treatment with human platelets, an exogenous source of growth factors, was not accompanied by an increase in matrix IGF-I, IGF-II, or TGF-beta 1 label, suggesting a particular effect of estradiol to facilitate this process. Because growth factors in bone matrix may act as coupling agents when released during resorption, reduced growth factor incorporation in the presence of reduced sex steroid concentrations may lead to uncoupling of resorption and subsequent formation.

scholarly journals Transforming growth factor beta 1 (TGF-beta 1) induced neutrophil recruitment to synovial tissues: implications for TGF-beta-driven synovial inflammation and hyperplasia.

1991 ◽  
Vol 173 (5) ◽  
pp. 1121-1132 ◽  
Author(s):  
R A Fava ◽  
N J Olsen ◽  
A E Postlethwaite ◽  
K N Broadley ◽  
J M Davidson ◽  
...  
Keyword(s):  
Growth Factor ◽  
Synovial Tissue ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Biologically Active ◽  
Tgf Beta ◽  
Histological Techniques ◽  
Growth Factor Beta

We have studied the consequences of introducing human recombinant transforming growth factor beta 1 (hrTGF-beta 1) into synovial tissue of the rat, to begin to better understand the significance of the fact that biologically active TGF-beta is found in human arthritic synovial effusions. Within 4-6 h after the intra-articular injection of 1 microgram of hrTGF-beta 1 into rat knee joints, extensive recruitment of polymorphonuclear leukocytes (PMNs) was observed. Cytochemistry and high resolution histological techniques were used to quantitate the influx of PMNs, which peaked 6 h post-injection. In a Boyden chamber assay, hrTGF-beta 1 at 1-10 fg/ml elicited a chemotactic response from PMNs greater in magnitude than that evoked by FMLP, establishing that TGF-beta 1 is an effective chemotactic agent for PMNs in vitro as well as in vivo. That PMNs may represent an important source of TGF-beta in inflammatory infiltrates was strongly suggested by a demonstration that stored TGF-beta 1 was secreted during phorbol myristate acetate-stimulated degranulation in vitro. Acid/ethanol extracts of human PMNs assayed by ELISA contained an average of 355 ng of TGF/beta 1 per 10(9) cells potentially available for secretion during degranulation of PMNs. [3H]Thymidine incorporation in vivo and autoradiography of tissue sections revealed that widespread cell proliferation was triggered by TGF-beta 1 injection. Synovial lining cells and cells located deep within the subsynovial connective tissue were identified as sources of at least some of the new cells that contribute to TGF-beta 1-induced hyperplasia. Our results demonstrate that TGF-beta is capable of exerting pathogenic effects on synovial tissue and that PMNs may represent a significant source of the TGF-beta present in synovial effusions.

scholarly journals Regulation of Trypanosoma cruzi infections in vitro and in vivo by transforming growth factor beta (TGF-beta).

1991 ◽  
Vol 174 (3) ◽  
pp. 539-545 ◽  
Author(s):  
J S Silva ◽  
D R Twardzik ◽  
S G Reed
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Tgf Beta ◽  
Ifn Gamma ◽  
Human Macrophages ◽  
Growth Factor Beta ◽  
Cruzi Infection

The effects of transforming growth factor beta (TGF-beta) on interferon gamma-mediated killing of the intracellular protozoan parasite Trypanosoma cruzi and on the course of T. cruzi infection in mice were investigated. Spleen cells from mice with acute T. cruzi infections were found to produce elevated levels of biologically active TGF-beta in vitro, and the possibility that TGF-beta may mediate certain aspects of T. cruzi infection was then addressed. When mouse peritoneal macrophages were treated with TGF-beta in vitro, the ability of IFN-gamma to activate intracellular inhibition of the parasite was blocked. This occurred whether cells were treated with TGF-beta either before or after IFN-gamma treatment. TGF-beta treatment also blocked the T. cruzi-inhibiting effects of IGN-gamma on human macrophages. Additionally, treatment of human macrophages with TGF-beta alone led to increased parasite replication in these cells. The effects of TGF-beta on T. cruzi infection in vivo were then investigated. Susceptible C57BL/6 mice developed higher parasitemias and died earlier when treated with TGF-beta during the course of infection. Resistant C57BL/6 x DBA/2 F1 mice treated with TGF-beta also had increased parasitemias, and 50% mortality, compared with no mortality in infected, saline-treated controls. A single dose of TGF-beta, given at the time of infection, was sufficient to significantly decrease resistance to infection in F1 mice and to exacerbate infection in susceptible C57BL/6 mice. Furthermore, a single injection of TGF-beta was sufficient to counter the in vivo protective effects of IFN-gamma. We conclude that TGF-beta, produced during acute T. cruzi infection in mice, is a potent inhibitor of the effects of macrophage activating cytokines in vivo and in vitro and may play a role in regulating infection.

Growth factor and somatic cell regulation of mouse gonocyte-derived colony formation in vitro

Reproduction ◽  
2000 ◽  
pp. 85-91 ◽  
Author(s):  
S Hasthorpe ◽  
S Barbic ◽  
PJ Farmer ◽  
JM Hutson
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Colony Formation ◽  
Inhibitory Action ◽  
Transforming Growth Factor ◽  
Epidermal Growth ◽  
Growth Factor Beta

At birth, the mouse gonocyte does not resume mitotic activity for several days in vivo but, in an in vitro clonogenic system, cell division commences soon after culture. Somatic testis cell underlays had potent inhibitory activity on gonocyte-derived colony formation (23 +/- 15% compared with 84 +/- 1% in controls; P = 0.0001) when added to cultures of gonocytes in vitro. A Sertoli cell line, TM4B, had an even more pronounced effect on gonocyte clonogenic capacity, with 1 +/- 1% compared with 72 +/- 17% colony formation in controls (P = 0.0003). Testis cells appeared to have a direct inhibitory effect since testis-conditioned medium did not show a significant reduction in the number of colonies. The observed reduction in colony formation with the testis cell underlay was not accounted for by decreased attachment of gonocytes as simultaneous addition of a single cell suspension of testis cells was still effective in significantly reducing colony number when compared with controls (P = 0.01). Therefore, the observed inhibition exerted by testis cells appears to be a consequence of decreased proliferation of gonocytes. Growth factors belonging to the transforming growth factor beta superfamily which are known to be expressed in testis, such as transforming growth factor beta and epidermal growth factor, did not exert any inhibitory action on gonocyte-derived colony formation when added together or alone. However, a shift to a smaller colony size occurred in the presence of transforming growth factor beta and transforming growth factor beta plus epidermal growth factor, indicating a reduction in colony cell proliferation. Evidence for the expression of the Mullerian inhibiting substance receptor on newborn gonocytes using in situ hybridization was inconclusive. This finding was in agreement with the lack of a direct action of Mullerian inhibiting substance on the formation of gonocyte-derived colonies in vitro. Leukaemia inhibitory factor, alone or in combination with forskolin, had neither an inhibitory nor an enhancing effect on gonocyte-derived colony formation. An in vitro clonogenic method to assay for the proliferation of gonocytes in the presence of specific growth factors, cell lines, testis cell underlays and cell suspensions was used to identify a somatic cell-mediated inhibitor which may be responsible for the inhibitory action on gonocyte proliferation in vivo shortly after birth.

scholarly journals Immunoregulatory role of transforming growth factor beta (TGF-beta) in development of killer cells: comparison of active and latent TGF-beta 1.

1990 ◽  
Vol 172 (6) ◽  
pp. 1777-1784 ◽  
Author(s):  
S C Wallick ◽  
I S Figari ◽  
R E Morris ◽  
A D Levinson ◽  
M A Palladino
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Recombinant Dna ◽  
Chinese Hamster ◽  
Tgf Beta ◽  
Recombinant Dna Technology ◽  
Growth Factor Beta

Using recombinant DNA technology, we have generated Chinese hamster ovary (CHO) cell lines that synthesize latent transforming growth factor beta 1 (TGF-beta 1) to study immune regulation by TGF-beta 1. In vitro, latent TGF-beta 1 synthesized by transfectants or added exogenously as a purified complex after activation inhibited CTL generation to a similar extent as seen with acid-activated recombinant human (rHu) TGF-beta 1. In vivo, serum from nu/nu mice bearing CHO/TGF-beta 1 tumors contained significant levels of latent TGF-beta 1 in addition to depressed natural killer (NK) activity in spleens which paralleled that seen in C3H/HeJ mice treated with acid-activated rHuTGF-beta 1. rHuTGF-beta 1 treatment of mice receiving heart allografts resulted in significant enhancement of organ graft survival. Because of possible regulated tissue-specific activation, administration of latent rather than active TGF-beta may provide a better route to deliver this powerful immunosuppressive agent in vivo.

Well-defined growth factors promote cardiac development in axolotl mesodermal explants

Development ◽  
1991 ◽  
Vol 112 (4) ◽  
pp. 1095-1101
Author(s):  
A.J. Muslin ◽  
L.T. Williams
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Cardiac Tissue ◽  
Transforming Growth Factor ◽  
Cardiac Development ◽  
Ambystoma Mexicanum ◽  
Tgf Beta ◽  
Cardiac Mesoderm

The effect of growth factors on the formation of cardiac mesoderm in the urodele, Ambystoma mexicanum (axolotl), has been examined using an in vitro explant system. It has previously been shown that cardiac mesoderm is induced by pharyngeal endoderm during neurula stages in urodeles. In this study, explants of prospective cardiac mesoderm from early neurula stage embryos rarely formed beating cardiac tissue in culture. When transforming growth factor beta-1 (TGF-beta 1) or platelet-derived growth factor BB (PDGF) was added to such explants, the frequency of heart tissue formation increased markedly. The addition of other growth factors to these explants did not enhance cardiac mesoderm formation. The addition of basic fibroblast growth factor (bFGF) to prospective heart mesoderm derived from later stage embryos resulted in a decreased tendency to form cardiac tissue. These results suggest that growth factors analogous to TGF-beta 1, PDGF, and bFGF may regulate the initial stages of vertebrate cardiac development in vivo.

A GC-rich domain with bifunctional effects on mRNA and protein levels: implications for control of transforming growth factor beta 1 expression

1993 ◽  
Vol 13 (6) ◽  
pp. 3588-3597
Author(s):  
L Scotto ◽  
R K Assoian
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Mrna Levels ◽  
Tgf Beta ◽  
Rich Domain ◽  
Growth Factor Beta

Chimeric plasmids containing selected reporter coding domains and portions of the transforming growth factor beta 1 (TGF-beta 1) 3' untranslated region (UTR) were prepared and used to identify potential mechanisms involved in regulating the biosynthesis of TGF-beta 1. Transient transfections with core and chimeric constructs containing the chloramphenicol acetyltransferase (CAT) reporter showed that steady-state CAT mRNA levels were decreased two- to threefold in response to the TGF-beta 1 3' UTR. Interestingly, CAT activity was somewhat increased in the same transfectants. Thus, production of CAT protein per unit of mRNA was stimulated by the TGF-beta 1 3' UTR (approximately fourfold in three cell lines of distinct lineage). The translation-stimulatory effect of the TGF-beta 1 3' UTR suggested by these studies in vivo was confirmed in vitro by cell-free translation of core and chimeric transcripts containing the growth hormone coding domain. These studies showed that production of growth hormone was stimulated threefold by the TGF-beta 1 3' UTR. A deletion analysis in vivo indicated that the GC-rich domain in the TGF-beta 1 3' UTR was responsible for both the decrease in mRNA levels and stimulation of CAT activity-mRNA. We conclude that this GC-rich domain can have a bifunctional effect on overall protein expression. Moreover, the notable absence of this GC-rich domain in TGF-beta 2, TGF-beta 3, TGF-beta 4, and TGF-beta 5 indicates that expression of distinct TGF-beta family members can be differentially controlled in cells.

scholarly journals A GC-rich domain with bifunctional effects on mRNA and protein levels: implications for control of transforming growth factor beta 1 expression.

1993 ◽  
Vol 13 (6) ◽  
pp. 3588-3597 ◽  
Author(s):  
L Scotto ◽  
R K Assoian
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Mrna Levels ◽  
Tgf Beta ◽  
Rich Domain ◽  
Growth Factor Beta

Chimeric plasmids containing selected reporter coding domains and portions of the transforming growth factor beta 1 (TGF-beta 1) 3' untranslated region (UTR) were prepared and used to identify potential mechanisms involved in regulating the biosynthesis of TGF-beta 1. Transient transfections with core and chimeric constructs containing the chloramphenicol acetyltransferase (CAT) reporter showed that steady-state CAT mRNA levels were decreased two- to threefold in response to the TGF-beta 1 3' UTR. Interestingly, CAT activity was somewhat increased in the same transfectants. Thus, production of CAT protein per unit of mRNA was stimulated by the TGF-beta 1 3' UTR (approximately fourfold in three cell lines of distinct lineage). The translation-stimulatory effect of the TGF-beta 1 3' UTR suggested by these studies in vivo was confirmed in vitro by cell-free translation of core and chimeric transcripts containing the growth hormone coding domain. These studies showed that production of growth hormone was stimulated threefold by the TGF-beta 1 3' UTR. A deletion analysis in vivo indicated that the GC-rich domain in the TGF-beta 1 3' UTR was responsible for both the decrease in mRNA levels and stimulation of CAT activity-mRNA. We conclude that this GC-rich domain can have a bifunctional effect on overall protein expression. Moreover, the notable absence of this GC-rich domain in TGF-beta 2, TGF-beta 3, TGF-beta 4, and TGF-beta 5 indicates that expression of distinct TGF-beta family members can be differentially controlled in cells.

scholarly journals Adherence-dependent increase in human monocyte PDGF(B) mRNA is associated with increases in c-fos, c-jun, and EGR2 mRNA.

1990 ◽  
Vol 111 (5) ◽  
pp. 2139-2148 ◽  
Author(s):  
R J Shaw ◽  
D E Doherty ◽  
A G Ritter ◽  
S H Benedict ◽  
R A Clark
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Gene Activation ◽  
Cytochalasin D ◽  
Tgf Beta ◽  
Mrna Accumulation ◽  
Tissue Macrophage

Adherence is an important initial step in the transition of a circulating monocyte to a tissue macrophage. This differentiation is accompanied by an augmented capacity to generate growth factors. We hypothesized that adherence itself might be an important trigger for a sequence of gene activation culminating in cells with increased mRNA encoding profibrotic growth factors such as platelet-derived growth factor B subunit (PDGF[B]) and transforming growth factor-beta (TGF-beta). After in vitro adherence, human monocytes had a biphasic increase in PDGF(B) mRNA with peaks at 6 h and 13 d. No increase in TGF-beta mRNA was observed. The 6-h increase in PDGF(B) mRNA was adherence dependent, and in addition, was abrogated when the cytoskeletal integrity was compromised by cytochalasin D. The 6-h increase in PDGF(B) mRNA was unaltered by adherence in the presence of the monocyte stimulus lipopolysaccharide. Adherence to either fibronectin or collagen-coated plastic had little consistent effect on PDGF(B) mRNA accumulation. The increased PDGF(B) mRNA observed in adherent monocytes was accompanied by increases in mRNAs of the early growth response genes c-fos (maximal at 20 min), c-jun, and EGR2 (maximal at 6-24 h). The increase in c-jun and EGR2, but not c-fos, mRNA was also abrogated by cytochalasin D. These observations suggest that adherence results in increases of c-fos, c-jun, EGR2, and PDGF(B) mRNA. In addition, the increases in c-jun, EGR2, and PDGF(B) may depend on cytoskeletal rearrangement. Modulation of these events at the time of adherence offers a mechanism by which differential priming of the cells may be accomplished.

scholarly journals Autoantibodies produced spontaneously by young 1pr mice carry transforming growth factor beta and suppress cytotoxic T lymphocyte responses.

1995 ◽  
Vol 181 (5) ◽  
pp. 1875-1880 ◽  
Author(s):  
D A Rowley ◽  
E T Becken ◽  
R M Stach
Keyword(s):  
Growth Factor ◽  
T Lymphocyte ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Cytotoxic T Lymphocyte ◽  
Tgf Beta ◽  
Growth Factor Beta ◽  
Ctl Responses

Young MRL/MPJ-lpr (lpr) mice 8-12 wk old challenged with alloantigen had significantly lower specific cytolytic T lymphocyte (CTL) responses than control MRL/MPJ +/+ mice. Serum from lpr mice compared with serum from ++ or normal C3H mice powerfully suppressed CTL responses in mixed lymphocyte cultures (MLC); absorbing lpr serum on protein G, adding antibody against transforming growth factor beta (TGF-beta) to cultures or dissociating immunoglobulin G (IgG) and TGF-beta before additions to cultures prevented suppression. Apparently autoantibody, similar to IgG produced by normal mice in response to immunization, carries TGF-beta which suppresses CTL responses in vivo and in vitro.

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