AGE-DEPENDENT EXPRESSION OF TRANSFORMING GROWTH FACTOR β1 (TGF-β1) AND ITS RECEPTORS, AND AGE-RELATED STIMULATORY EFFECT OF TGF-β1 ON PROTEOGLYCAN SYNTHESIS IN RAT INTERVERTEBRAL DISCS

Age-related alterations of gene expression of transforming growth factor β1 (TGF-β1) and its receptors ( T β Rs ) in tissues derived from rat intervertebral discs were assessed together with TGF-β1-dependent proteoglycan synthesis by the cultured disc cells. Disc tissues and cells were individually harvested from two sites of the coccygeal vertebrae, namely the nucleus pulposus (NP) and annulus fibrosus (AF), which are major distinct components of the intervertebral discs. Semi-quantitative RT-PCR analysis indicated that the level of gene expression of TGF-β1/TGF-β1 receptor type I (TβR-I) of NP decreased with age. In AF, the level of TGF-β1/ T β Rs gene expression did not apparently differ with age. Consistent with the RT-PCR results, stimulation of proteoglycan synthesis by TGF-β1 in NP cells decreased with age. Proteoglycan synthesis by AF cells was also stimulated by TGF-β1. However, levels of this stimulation by AF cells were identical. The present findings indicate that the genetic expression of TGF-β1/ T β R -I and TGF-β1-dependent proteoglycan synthesis decreased with age in NP cells, and further suggest that a loss of proteoglycan synthesis with age in the intervertebral disc is at least in part due to the transcriptional down regulation of TGF-β1/ T βR-I and decreased synthetic ability of proteoglycans in response to TGF-β1 by NP cells.

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Transforming growth factor-β1 up-regulates connexin43 expression in osteocytes via canonical Smad-dependent signaling pathway

Bioscience Reports ◽

10.1042/bsr20181678 ◽

2018 ◽

Vol 38 (6) ◽

Cited By ~ 8

Author(s):

Wenjing Liu ◽

Yujia Cui ◽

Jianxun Sun ◽

Linyi Cai ◽

Jing Xie ◽

...

Keyword(s):

Growth Factor ◽

Connexin 43 ◽

Transforming Growth Factor ◽

Bone Cells ◽

Underlying Mechanism ◽

Transforming Growth Factor Β1 ◽

Type I ◽

Gap Junctional Intercellular Communication ◽

Cx43 Expression ◽

Tgf Β1

Connexin 43 (Cx43)-mediated gap junctional intercellular communication (GJIC) has been shown to be important in regulating multiple functions of bone cells. Transforming growth factor-β1 (TGF-β1) exhibited controversial effects on the expression of Cx43 in different cell types. To date, the effect of TGF-β1 on the Cx43 expression of osteocytes is still unknown. In the present study, we detected the expression of TGF-β1 in osteocytes and bone tissue, and then used recombinant mouse TGF-β1 to elucidate its effect on gap junctions (GJs) of osteocytes. Our data indicated that TGF-β1 up-regulated both mRNA and protein expression of Cx43 in osteocytes. Together with down-regulation of Cx43 expression after being treated with TGF-β type I receptor inhibitor Repsox, we deduced that TGF-β1 can positively regulate Cx43 expression in osteocytes. Thus we next focussed on the downstream signals of TGF-β and found that TGF-β1-mediated smads, Smad3 and Smad4, to translocate into nucleus. These translocated signal proteins bind to the promoter of Gja1 which was responsible for the changed expression of Cx43. The present study provides evidence that TGF-β1 can enhance GJIC between osteocytes through up-regulating Cx43 expression and the underlying mechanism involved in the activation of Smad-dependent pathway.

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Smad7 Abrogates Transforming Growth Factor-β1-mediated Growth Inhibition in COLO-357 Cells through Functional Inactivation of the Retinoblastoma Protein

Journal of Biological Chemistry ◽

10.1074/jbc.m500583200 ◽

2005 ◽

Vol 280 (23) ◽

pp. 21858-21866 ◽

Cited By ~ 28

Author(s):

Nichole Boyer Arnold ◽

Murray Korc

Keyword(s):

Growth Factor ◽

Growth Inhibition ◽

Transforming Growth Factor ◽

Nuclear Translocation ◽

Retinoblastoma Protein ◽

Transforming Growth Factor Β1 ◽

Type I ◽

Pancreatic Cancer Cells ◽

Induced Apoptosis ◽

Tgf Β1

Smad7 is overexpressed in 50% of human pancreatic cancers. COLO-357 pancreatic cancer cells engineered to overexpress Smad7 are resistant to the actions of transforming growth factor-β1 (TGF-β1) with respect to growth inhibition and cisplatin-induced apoptosis but not with respect to modulation of gene expression. To delineate the mechanisms underlying these divergent consequences of Smad7 overexpression, we studied the effects of Smad7 on TGF-β1-dependent signaling pathways and cell cycle regulating proteins. TGF-β1 induced the phosphorylation of MAPK, p38 MAPK, and AKT2 irrespective of the levels of Smad7, and inhibitors of these pathways did not alter TGF-β1 actions on cell growth. By contrast, Smad7 overexpression interfered with TGF-β1-mediated attenuation of cyclin A and B levels, inhibition of cdc2 dephosphorylation and CDK2 inactivation, up-regulation of p27, and the maintenance of the retinoblastoma protein (RB) in a hypophosphorylated state. Smad7 also suppressed TGF-β1-mediated inhibition of E2F activity but did not alter TGF-β1-mediated phosphorylation of Smad2, the nuclear translocation of Smad2/3/4, or DNA binding of the Smad2/3/4 complex. Although Smad7 did not associate with the type I TGF-β receptor (TβRI), SB-431542, an inhibitor of the kinase activity of this receptor, blocked TGF-β1-mediated effects on Smad-2 phosphorylation. These findings point toward a novel paradigm whereby Smad7 acts to functionally inactivate RB and de-repress E2F without blocking the activation of TβRI and the nuclear translocation of Smad2/3, thereby allowing for TGF-β1 to exert effects in a cancer cell that is resistant to TGF-β1-mediated growth inhibition.

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Transforming growth factor β1 regulates angiotensin II type I receptor gene expression in the extravillous trophoblast cell line SGHPL-4

MHR Basic science of reproductive medicine ◽

10.1093/molehr/gah242 ◽

2005 ◽

Vol 11 (12) ◽

pp. 847-852 ◽

Cited By ~ 4

Author(s):

C.L. Tower ◽

S.L. Chappell ◽

K. Morgan ◽

N. Kalsheker ◽

P.N. Baker ◽

...

Keyword(s):

Gene Expression ◽

Growth Factor ◽

Transforming Growth Factor ◽

Receptor Gene ◽

Transforming Growth Factor Β1 ◽

Trophoblast Cell ◽

Extravillous Trophoblast ◽

Type I ◽

Receptor Gene Expression ◽

Trophoblast Cell Line

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Overexpression of Transforming Growth Factor β1 in Malignant Prostate Cells is Partly Caused by a Runaway of TGF-β1 Auto-induction Mediated Through a Defective Recruitment of Protein Phosphatase 2A by TGF-β Type I Receptor

Urology ◽

10.1016/j.urology.2010.03.061 ◽

2010 ◽

Vol 76 (6) ◽

pp. 1519.e8-1519.e13 ◽

Cited By ~ 11

Author(s):

Nengwang Yu ◽

James M. Kozlowski ◽

Irwin I. Park ◽

Lin Chen ◽

Qiang Zhang ◽

...

Keyword(s):

Growth Factor ◽

Protein Phosphatase ◽

Transforming Growth Factor ◽

Protein Phosphatase 2A ◽

Transforming Growth Factor Β1 ◽

Type I ◽

Prostate Cells ◽

Phosphatase 2A ◽

Malignant Prostate ◽

Tgf Β1

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Decreased MiR-30a promotes TGF-β1-mediated arachnoid fibrosis in post-hemorrhagic hydrocephalus

Translational Neuroscience ◽

10.1515/tnsci-2020-0010 ◽

2020 ◽

Vol 11 (1) ◽

pp. 60-74

Author(s):

Chaohong Zhan ◽

Gelei Xiao ◽

Xiangyang Zhang ◽

Xiaoyu Chen ◽

Zhiping Zhang ◽

...

Keyword(s):

Growth Factor ◽

Intraventricular Hemorrhage ◽

Type I Collagen ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β1 ◽

Ventricular System ◽

Type I ◽

Cerebral Ventricles ◽

The Right ◽

Tgf Β1

AbstractBackgroundFibrosis in the ventricular system is closely associated with post-hemorrhagic hydrocephalus (PHH). It is characterized by an expansion of the cerebral ventricles due to CSF accumulation following intraventricular hemorrhage (IVH). The activation of transforming growth factor-β1 (TGF-β1) may be involved in thrombin-induced arachnoid fibrosis.MethodsA rat model of PHH was established by injection of autologous non-anticoagulated blood from the right femoral artery into the lateral ventricles. Differential expression of miR-30a was detected in rat arachnoid cells by RNA sequencing. AP-1, c-Fos, and TRAF3IP2 were knocked down in primary arachnoid cells, and the degree of arachnoid fibrosis was assessed.ResultsDecreased expression of miR-30a and increased expression of TRAF3IP2, TGF-β1, and α-SMA were detected in the arachnoid cells of PHH rat. Besides, overexpression of miR-30a targets TRAF3IP2 mRNA 3′UTR and inhibits the expression of TRAF3IP2, TGF-β1, and α-SMA in the primary arachnoid cells. Furthermore, TRAF3IP2 activates AP-1 to promote arachnoid fibrosis. The content of type I collagen in the primary arachnoid cells was reduced after the silencing of AP-1 and TRAF3IP2.ConclusionsThis study identified a miR-30a-regulated mechanism of arachnoid fibrosis, suggesting a previously unrecognized contribution of miR-30a to the pathogenesis of fibrosis in the ventricular system. These results might provide a new target for the clinical diagnosis and treatment of PHH.

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Circulating transforming growth factor-β1 facilitates remyelination in the adult central nervous system

eLife ◽

10.7554/elife.41869 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 11

Author(s):

Machika Hamaguchi ◽

Rieko Muramatsu ◽

Harutoshi Fujimura ◽

Hideki Mochizuki ◽

Hirotoshi Kataoka ◽

...

Keyword(s):

Growth Factor ◽

Adult Mouse ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β1 ◽

Demyelinating Diseases ◽

Mouse Serum ◽

Type I ◽

Therapeutic Possibility ◽

Functional Regeneration ◽

Tgf Β1

Oligodendrocyte maturation is necessary for functional regeneration in the CNS; however, the mechanisms by which the systemic environment regulates oligodendrocyte maturation is unclear. We found that Transforming growth factor (TGF)-β1, which is present in higher levels in the systemic environment, promotes oligodendrocyte maturation. Oligodendrocyte maturation was enhanced by adult mouse serum treatment via TGF-β type I receptor. Decrease in circulating TGF-β1 level prevented remyelination in the spinal cord after toxin-induced demyelination. TGF-β1 administration promoted remyelination and restored neurological function in a multiple sclerosis animal model. Furthermore, TGF-β1 treatment stimulated human oligodendrocyte maturation. These data provide the therapeutic possibility of TGF-β for demyelinating diseases.

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Transforming growth factor-β1 downregulation of Smad1 gene expression in rat hepatic stellate cells

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00436.2002 ◽

2003 ◽

Vol 285 (3) ◽

pp. G539-G546 ◽

Cited By ~ 42

Author(s):

Hong Shen ◽

Guojiang Huang ◽

Mohammed Hadi ◽

Patrick Choy ◽

Manna Zhang ◽

...

Keyword(s):

Gene Expression ◽

Growth Factor ◽

Hepatic Stellate Cells ◽

Intracellular Signaling ◽

Transforming Growth Factor ◽

Stellate Cells ◽

Transforming Growth Factor Β ◽

Transforming Growth Factor Β1 ◽

Dependent Manner ◽

Tgf Β1

Smads are intracellular signaling molecules of the transforming growth factor-β (TGF-β) superfamily that play an important role in the activation of hepatic stellate cells (HSCs) and hepatic fibrosis. Excepting the regulation of Smad7, receptor-regulated Smad gene expression is still unclear. We employed rat HSCs to investigate the expression and regulation of the Smad1 gene, which is a bone morphogenetic protein (BMP) receptor-regulated Smad. We found that the expression and phosphorylation of Smad1 are increased during the activation of HSCs. Moreover, TGF-β significantly inhibits Smad1 gene expression in HSCs in a time- and dose-dependent manner. Furthermore, although both TGF-β1 and BMP2 stimulate the activation of HSCs, they have different effects on HSC proliferation. In conclusion, Smad1 expression and phosphorylation are increased during the activation of HSCs and TGF-β1 significantly inhibits the expression of the Smad1 gene.

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TGF-β1 Increases GDNF Production by Upregulating the Expression of GDNF and Furin in Human Granulosa-Lutein Cells

Cells ◽

10.3390/cells9010185 ◽

2020 ◽

Vol 9 (1) ◽

pp. 185 ◽

Cited By ~ 6

Author(s):

Jingwen Yin ◽

Hsun-Ming Chang ◽

Yuyin Yi ◽

Yuanqing Yao ◽

Peter C.K. Leung

Keyword(s):

Growth Factor ◽

Cell Line ◽

Kinase Inhibitors ◽

Transforming Growth Factor ◽

Biological Response ◽

Follicular Development ◽

Transforming Growth Factor Β1 ◽

Type I ◽

High Level ◽

Tgf Β1

Glial cell line-derived neurotrophic factor (GDNF) is expressed at a high level in the human ovary and GDNF signaling is involved in the direct control of follicular activation and oocyte maturation. Transforming growth factor-β1 (TGF-β1) plays an important role in the regulation of various ovarian functions. Furin is an intracellular serine endopeptidase of the subtilisin family that is closely associated with the activation of multiple protein precursors. Despite the important roles of GDNF and TGF-β1 in the regulation of follicular development, whether TGF-β is able to regulate the expression and production of GDNF in human granulosa cells remains to be determined. The aim of this study was to investigate the effect of TGF-β1 on the production of GDNF and its underlying mechanisms in human granulosa-lutein (hGL) cells. We used two types of hGL cells (primary hGL cells and an established immortalized hGL cell line, SVOG cells) as study models. Our results show that TGF-β1 significantly induced the expression of GDNF and furin, which, in turn, increased the production of mature GDNF. Using a dual inhibition approach combining RNA interference and kinase inhibitors against cell signaling components, we showed that the TβRII type II receptor and ALK5 type I receptor are the principal receptors that mediated TGF-β1-induced cellular activity in hGL cells. Additionally, Sma- and Mad-related protein (SMAD)3 and SMAD4 are the downstream signaling transducers that mediate the biological response induced by TGF-β1. Furthermore, furin is the main proprotein convertase that induces the production of GDNF. These findings provide additional regulatory mechanisms by which an intrafollicular factor influences the production of another growth factor through a paracrine or autocrine interaction in hGL cells.

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