Transforming Growth Factor-β1 Impairs Endothelin-1-Mediated Contraction of Brain Vessels by Inducing Mitogen-Activated Protein (MAP) Kinase Phosphatase-1 and Inhibiting p38 MAP Kinase

2007 ◽  
Vol 72 (6) ◽  
pp. 1476-1483 ◽  
Author(s):  
Xin-Kang Tong ◽  
Edith Hamel
Keyword(s):  
Growth Factor ◽  
Map Kinase ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
P38 Map Kinase ◽  
Brain Vessels ◽  
Endothelin 1 ◽  
Map Kinase Phosphatase ◽  
Protein Map ◽  
Mitogen Activated Protein

scholarly journals MAP Kinase Phosphatase-1 Protects against Inflammatory Bone Loss

2009 ◽  
Vol 88 (12) ◽  
pp. 1125-1130 ◽  
Author(s):  
R. Sartori ◽  
F. Li ◽  
K.L. Kirkwood
Keyword(s):  
Bone Loss ◽  
Map Kinase ◽  
Map Kinases ◽  
Group Analysis ◽  
P38 Map Kinase ◽  
Wild Type ◽  
Map Kinase Phosphatase ◽  
Tnf Α ◽  
Protein Map ◽  
Mitogen Activated Protein

The mitogen-activated protein (MAP) kinase phosphatase (MKP) family plays an important function in regulating the pro-inflammatory cytokines by deactivating MAP kinases. MKP-1 is essential for the dephosphorylation of p38 MAP kinase that regulates expression of IL-6, TNF-α, and IL-1β. We hypothesized that MKP-1 regulates inflammatory bone loss in experimental periodontitis. Wild-type and Mkp-1−/− mice received A. actinomycetemcomitans LPS injection in the palatal region or PBS control 3 times/wk for 30 days. Mice were killed, and maxillae were assessed by microcomputed tomography, histological analysis, and TRAP staining for measurement of bone loss, extent of inflammation, and degree of osteoclastogenesis. Results indicated that, in LPS-injected Mkp-1−/− mice, significantly greater bone loss occurred with more inflammatory infiltrate and a significant increase in osteoclastogenesis compared with Mkp-1−/− control sites or either wild-type group. Analysis of these data indicates that MKP-1 plays a key role in the regulation of inflammatory bone loss.

scholarly journals Catalytic activation of mitogen-activated protein (MAP) kinase phosphatase-1 by binding to p38 MAP kinase: critical role of the p38 C-terminal domain in its negative regulation

2000 ◽  
Vol 352 (1) ◽  
pp. 155-163 ◽  
Author(s):  
Dorothy HUTTER ◽  
Peili CHEN ◽  
Janice BARNES ◽  
Yusen LIU
Keyword(s):  
Catalytic Activity ◽  
Feedback Control ◽  
Map Kinase ◽  
Regulatory Mechanism ◽  
Critical Role ◽  
P38 Map Kinase ◽  
Catalytic Activation ◽  
Map Kinase Phosphatase ◽  
Protein Map ◽  
Mitogen Activated Protein

Mitogen-activated protein (MAP) kinase phosphatase-1 (MKP-1) is the archetypal member of the dual-specificity protein phosphatase family, the expression of which can be rapidly induced by a variety of growth factors and cellular stress. Since MKP-1 protein localizes in the nucleus, it has been suggested to play an important role in the feedback control of MAP kinase-regulated gene transcription. Recently it has been demonstrated that the interaction of several cytosolic MAP kinase phosphatases with MAP kinases can trigger the catalytic activation of the phosphatases. It is unclear whether such a regulatory mechanism can apply to nuclear MAP kinase phosphatases and serve as an additional apparatus for the feedback control of MAP kinase-mediated gene expression. Here we have shown that MKP-1 associates directly with p38 MAP kinase both in vivo and in vitro, and that this interaction enhances the catalytic activity of MKP-1. The point mutation Asp-316 → Asn in the C-terminus of p38, analogous to the ERK2 (extracellular-signal-regulated kinase 2) sevenmaker mutation, dramatically decreases its binding to MKP-1 and substantially compromises its stimulatory effect on the catalytic activity of this phosphatase. Consistent with its defective interaction with MKP-1, this p38 mutant also displays greater resistance to dephosphorylation by the phosphatase. Our studies provide the first example of catalytic activation of a nuclear MAP kinase phosphatase through direct binding to a MAP kinase, suggesting that such a regulatory mechanism may play an important role in the feedback control of MAP kinase signalling in the nuclear compartment.

scholarly journals HSP22 (HSPB8) positively regulates PGF2α-induced synthesis of interleukin-6 and vascular endothelial growth factor in osteoblasts

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Gen Kuroyanagi ◽  
Go Sakai ◽  
Takanobu Otsuka ◽  
Naohiro Yamamoto ◽  
Kazuhiko Fujita ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Map Kinase ◽  
Interleukin 6 ◽  
Prostaglandin F2α ◽  
P38 Map Kinase ◽  
Vascular Endothelial ◽  
Mitogen Activated Protein ◽  
Endothelial Growth Factor ◽  
Vegf Release

Abstract Background Heat shock protein 22 (HSP22) belongs to class I of the small HSP family that displays ubiquitous expression in osteoblasts. We previously demonstrated that prostaglandin F2α (PGF2α), a potent bone remodeling factor, induces the synthesis of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) via p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether HSP22 is implicated in the PGF2α-induced synthesis of IL-6 and VEGF and the mechanism of MC3T3-E1 cells. Methods MC3T3-E1 cells were transfected with HSP22-siRNA. IL-6 and VEGF release was assessed by ELISA. Phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was detected by Western blotting. Results The PGF2α-induced release of IL-6 in HSP22 knockdown cells was significantly suppressed compared with that in the control cells. HSP22 knockdown also reduced the VEGF release by PGF2α. Phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was attenuated by HSP22 downregulation. Conclusions Our results strongly suggest that HSP22 acts as a positive regulator in the PGF2α-induced synthesis of IL-6 and VEGF in osteoblasts.

Incretins Enhance PGF2α-Induced Synthesis of IL-6 and Osteoprotegerin in Osteoblasts

2022 ◽  
Vol 54 (01) ◽  
pp. 42-49
Author(s):  
Tomoyuki Hioki ◽  
Gen Kuroyanagi ◽  
Kazuhiko Fujita ◽  
Go Sakai ◽  
Tetsu Kawabata ◽  
...  
Keyword(s):  
Map Kinase ◽  
Prostaglandin F2α ◽  
P38 Map Kinase ◽  
Β Cells ◽  
Kinase C ◽  
Protein Map ◽  
Mitogen Activated Protein ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

AbstractIncretins including glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), which are secreted from the small intestine after oral food ingestion, are currently well-known to stimulate insulin secretion from pancreatic β-cells and used for the treatment of type 2 diabetes mellitus. We have previously reported that prostaglandin F2α (PGF2α) stimulates the synthesis of interleukin-6 (IL-6) and osteoprotegerin in osteoblast-like MC3T3-E1 cells, and that IL-6 and osteoprotegerin release are mediated through the p44/p42 mitogen-activated protein (MAP) kinase, p38 MAP kinase or stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) pathways. In the present study, we investigated the effects of incretins including GLP-1 and GIP, on the PGF2α-induced synthesis of IL-6 and osteoprotegerin and examined the detailed mechanism in osteoblast-like MC3T3-E1 cells. We found that GIP and GLP-1 significantly stimulated the PGF2α-induced synthesis of IL-6 in osteoblast-like MC3T3-E1 cells. In addition, GIP and GLP-1 significantly enhanced the PGF2α-induced mRNA expression levels of IL-6. On the other hand, GIP and GLP-1 markedly stimulated the PGF2α-induced synthesis of osteoprotegerin. However, the phosphorylation of p44/p42 MAP kinase, p38 MAP kinase, or JNK induced by PGF2α was not affected by GIP or GLP-1. Therefore, these results strongly suggest that incretins enhance the PGF2α-induced synthesis of IL-6 and osteoprotegerin in osteoblast-like MC3T3-E1 cells. However, these syntheses are not mediated through p44/p42 MAP kinase, p38 MAP kinase, or JNK pathways.

scholarly journals p38 MAP Kinase Inhibitor Suppresses Transforming Growth Factor-β2–Induced Type 1 Collagen Production in Trabecular Meshwork Cells

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0120774 ◽  
Author(s):  
Miyuki Inoue-Mochita ◽  
Toshihiro Inoue ◽  
Tomokazu Fujimoto ◽  
Takanori Kameda ◽  
Nanako Awai-Kasaoka ◽  
...  
Keyword(s):  
Growth Factor ◽  
Map Kinase ◽  
Trabecular Meshwork ◽  
Transforming Growth Factor ◽  
Kinase Inhibitor ◽  
P38 Map Kinase ◽  
Collagen Production ◽  
Trabecular Meshwork Cells ◽  
Transforming Growth Factor Β2
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