Biomechanic and histologic analysis of fibroblastic effects of tendon-to-bone healing by transforming growth factor β1 (TGF-β1) in rotator cuff tears

Transforming growth factor-β1 (TGF-β1)-induced myofibroblast transdifferentiation from orbital fibroblasts is known to dominate tissue remodeling and fibrosis in Graves’ ophthalmopathy (GO). However, the signaling pathways through which TGF-β1 activates Graves’ orbital fibroblasts remain unclear. This study investigated the role of the mitogen-activated protein kinase (MAPK) pathway in TGF-β1-induced myofibroblast transdifferentiation in human Graves’ orbital fibroblasts. The MAPK pathway was assessed by measuring the phosphorylation of p38, c-Jun N-terminal kinase (JNK), and extracellular-signal-regulated kinase (ERK) by Western blots. The expression of connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), and fibronectin representing fibrogenesis was estimated. The activities of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) responsible for extracellular matrix (ECM) metabolism were analyzed. Specific pharmacologic kinase inhibitors were used to confirm the involvement of the MAPK pathway. After treatment with TGF-β1, the phosphorylation levels of p38 and JNK, but not ERK, were increased. CTGF, α-SMA, and fibronectin, as well as TIMP-1 and TIMP-3, were upregulated, whereas the activities of MMP-2/-9 were inhibited. The effects of TGF-β1 on the expression of these factors were eliminated by p38 and JNK inhibitors. The results suggested that TGF-β1 could induce myofibroblast transdifferentiation in human Graves’ orbital fibroblasts through the p38 and JNK pathways.

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Transforming growth factor-β1-induced N-cadherin drives cell–cell communication through connexin43 in osteoblast lineage

International Journal of Oral Science ◽

10.1038/s41368-021-00119-3 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Yueyi Yang ◽

Wenjing Liu ◽

JieYa Wei ◽

Yujia Cui ◽

Demao Zhang ◽

...

Keyword(s):

Growth Factor ◽

Gap Junction ◽

Cell Line ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β1 ◽

Cx43 Expression ◽

Mc3t3 Cell ◽

Primary Osteoblasts ◽

Tgf Β1 ◽

Cell Cell

AbstractGap junction (GJ) has been indicated to have an intimate correlation with adhesion junction. However, the direct interaction between them partially remains elusive. In the current study, we aimed to elucidate the role of N-cadherin, one of the core components in adhesion junction, in mediating connexin 43, one of the functional constituents in gap junction, via transforming growth factor-β1(TGF-β1) induction in osteoblasts. We first elucidated the expressions of N-cadherin induced by TGF-β1 and also confirmed the upregulation of Cx43, and the enhancement of functional gap junctional intercellular communication (GJIC) triggered by TGF-β1 in both primary osteoblasts and MC3T3 cell line. Colocalization analysis and Co-IP experimentation showed that N-cadherin interacts with Cx43 at the site of cell–cell contact. Knockdown of N-cadherin by siRNA interference decreased the Cx43 expression and abolished the promoting effect of TGF-β1 on Cx43. Functional GJICs in living primary osteoblasts and MC3T3 cell line were also reduced. TGF-β1-induced increase in N-cadherin and Cx43 was via Smad3 activation, whereas knockdown of Smad3 signaling by using siRNA decreased the expressions of both N-cadherin and Cx43. Overall, these data indicate the direct interactions between N-cadherin and Cx43, and reveal the intervention of adhesion junction in functional gap junction in living osteoblasts.

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Transforming Growth Factor-β1 (TGF-β1) Induces Mouse Precartilaginous Stem Cell Proliferation through TGF-β Receptor II (TGFRII)-Akt-β-Catenin Signaling

International Journal of Molecular Sciences ◽

10.3390/ijms150712665 ◽

2014 ◽

Vol 15 (7) ◽

pp. 12665-12676 ◽

Cited By ~ 9

Author(s):

Li Cheng ◽

Chengyu Zhang ◽

Ding Li ◽

Jian Zou ◽

Junfang Wang

Keyword(s):

Cell Proliferation ◽

Stem Cell ◽

Growth Factor ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β1 ◽

Stem Cell Proliferation ◽

Β Receptor ◽

Tgf Β1

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Transforming Growth Factor β1 (TGF-β1) Promotes Endothelial Cell Survival during In Vitro Angiogenesis via an Autocrine Mechanism Implicating TGF-α Signaling

Molecular and Cellular Biology ◽

10.1128/mcb.21.21.7218-7230.2001 ◽

2001 ◽

Vol 21 (21) ◽

pp. 7218-7230 ◽

Cited By ~ 145

Author(s):

Francesc Viñals ◽

Jacques Pouysségur

Keyword(s):

Endothelial Cells ◽

Growth Factor ◽

Cell Survival ◽

Network Formation ◽

Egf Receptor ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β1 ◽

In Vitro Angiogenesis ◽

Tgf Β1

ABSTRACT Mouse capillary endothelial cells (1G11 cell line) embedded in type I collagen gels undergo in vitro angiogenesis. Cells rapidly reorganize and form capillary-like structures when stimulated with serum. Transforming growth factor β1 (TGF-β1) alone can substitute for serum and induce cell survival and tubular network formation. This TGF-β1-mediated angiogenic activity depends on phosphatidylinositol 3-kinase (PI3K) and p42/p44 mitogen-activated protein kinase (MAPK) signaling. We showed that specific inhibitors of either pathway (wortmannin, LY-294002, and PD-98059) all suppressed TGF-β1-induced angiogenesis mainly by compromising cell survival. We established that TGF-β1 stimulated the expression of TGF-α mRNA and protein, the tyrosine phosphorylation of a 170-kDa membrane protein representing the epidermal growth factor (EGF) receptor, and the delayed activation of PI3K/Akt and p42/p44 MAPK. Moreover, we showed that all these TGF-β1-mediated signaling events, including tubular network formation, were suppressed by incubating TGF-β1-stimulated endothelial cells with a soluble form of an EGF receptor (ErbB-1) or tyrphostin AG1478, a specific blocker of EGF receptor tyrosine kinase. Finally, addition of TGF-α alone poorly stimulated angiogenesis; however, by reducing cell death, it strongly potentiated the action of TGF-β1. We therefore propose that TGF-β1 promotes angiogenesis at least in part via the autocrine secretion of TGF-α, a cell survival growth factor, activating PI3K/Akt and p42/p44 MAPK.

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Transforming Growth Factor β1 (TGF-β1) Suppresses Growth of B-cell Lymphoma Cells by p14ARF-dependent Regulation of Mutant p53

Journal of Biological Chemistry ◽

10.1074/jbc.m112.351411 ◽

2012 ◽

Vol 287 (27) ◽

pp. 23184-23195 ◽

Cited By ~ 7

Author(s):

Gang Chen ◽

Paritosh Ghosh ◽

Thomas O'Farrell ◽

Rachel Munk ◽

Louis J. Rezanka ◽

...

Keyword(s):

Growth Factor ◽

B Cell ◽

Transforming Growth Factor ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Transforming Growth Factor Β1 ◽

Mutant P53 ◽

Lymphoma Cells ◽

Tgf Β1

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Specificity protein 1 and Smad-dependent regulation of human heme oxygenase-1 gene by transforming growth factor-β1 in renal epithelial cells

AJP Renal Physiology ◽

10.1152/ajprenal.00519.2006 ◽

2007 ◽

Vol 293 (3) ◽

pp. F885-F894 ◽

Cited By ~ 16

Author(s):

Amie Traylor ◽

Thomas Hock ◽

Nathalie Hill-Kapturczak

Keyword(s):

Growth Factor ◽

Heme Oxygenase ◽

Transforming Growth Factor ◽

Tissue Injury ◽

Transforming Growth Factor Β1 ◽

Molecular Regulation ◽

Heme Oxygenase 1 ◽

Specificity Protein 1 ◽

Specificity Protein ◽

Tgf Β1

Excess transforming growth factor-β1 (TGF-β1) in the kidney leads to increased cell proliferation and deposition of extracellular matrix, resulting in progressive kidney fibrosis. TGF-β1, however, stabilizes and attenuates tissue injury through the activation of cytoprotective proteins, including heme oxygenase-1 (HO-1). HO-1 catabolizes pro-oxidant heme into substances with anti-oxidant, anti-apoptotic, anti-fibrogenic, vasodilatory and immune modulatory properties. Little is known regarding the molecular regulation of human HO-1 induction by TGF-β1 except that it is dependent on de novo RNA synthesis and requires a group of structurally related proteins called Smads. It is not known whether other DNA binding proteins are required to initiate transcription of HO-1 and, furthermore, the promoter region(s) involved in TGF-β1-mediated induction of HO-1 has not been identified. The purpose of this study was to further delineate the molecular regulation of HO-1 by TGF-β1 in human renal proximal tubular cells. Actinomycin D and nuclear run-on studies demonstrate that TGF-β1 augments HO-1 expression by increased gene transcription and does not involve increased mRNA stability. Using transient transfection, mithramycin A, small interfering RNA, electrophoretic mobility shift assays, and decoy oligonucleotide experiments, a TGF-β1-responsive region is identified between 9.1 and 9.4 kb of the human HO-1 promoter. This ∼280-bp TGF-β1-responsive region contains a putative Smad binding element and specificity protein 1 binding sites, both of which are required for human HO-1 induction by TGF-β1.

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Interleukin-13 and transforming growth factor-β1 inhibit spontaneous sleep in rabbits

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2000.279.3.r786 ◽

2000 ◽

Vol 279 (3) ◽

pp. R786-R792 ◽

Cited By ~ 17

Author(s):

Takeshi Kubota ◽

Jidong Fang ◽

Tetsuya Kushikata ◽

James M. Krueger

Keyword(s):

Growth Factor ◽

Proinflammatory Cytokines ◽

Transforming Growth Factor ◽

Inhibitory Effect ◽

Transforming Growth Factor Β1 ◽

Light Period ◽

Sleep Regulation ◽

Cytokine Network ◽

Physiological Sleep ◽

Tgf Β1

Proinflammatory cytokines, including interleukin-1β and tumor necrosis factor-α are involved in physiological sleep regulation. Interleukin (IL)-13 and transforming growth factor (TGF)-β1 are anti-inflammatory cytokines that inhibit proinflammatory cytokines by several mechanisms. Therefore, we hypothesized that IL-13 and TGF-β1 could attenuate sleep in rabbits. Three doses of IL-13 (8, 40, and 200 ng) and TGF-β1 (40, 100, and 200 ng) were injected intracerebroventricularly 3 h after the beginning of the light period. In addition, one dose of IL-13 (200 ng) and one dose of TGF-β1 (200 ng) were injected at dark onset. The two higher doses of IL-13 and the highest dose of TGF-β1 significantly inhibited spontanenous non-rapid eye movement sleep (NREMS) when they were given in the light period. IL-13 also inhibited NREMS after dark onset administration; however, the inhibitory effect was less potent than that observed after light period administration. The 40-ng dose of IL-13 inhibited REMS duration during the dark period. TGF-β1 administered at dark onset had no effect on sleep. These data provide additional evidence for the hypothesis that a brain cytokine network is involved in regulation of physiological sleep.

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