Hepatocyte growth factor-induced BMP-2 expression is mediated by c-Met receptor, FAK, JNK, Runx2, and p300 pathways in human osteoblasts

Tsai, Shu-Yao; Huang, Yuan‐Li; Yang, Wei-Hung; Tang, Chih‐Hsin

doi:10.1016/j.intimp.2012.03.026

Cited by 33 publications

(25 citation statements)

References 39 publications

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“…Our studies of these JNKi-treated DM mice provided similar results to those observed in the C66-treated DM mice. Activation of the JNK pathway can regulate recruitment of p300 and enhancement of histones H3 and H4 acetylation [43]. Accordingly, we concluded that the C66 treatment of diabetic mice down-regulates diabetes-increased p300/CBP expression and HATs activation via inactivation of JNK, and the subsequent histone hyperacetylation causes specific increases in the accumulation of p300/CBP at the promoters of CTGF, PAI-1 and FN-1 genes, as presented in Figure 8.…”

Section: Discussionmentioning

confidence: 86%

Novel curcumin analog C66 prevents diabetic nephropathy via JNK pathway with the involvement of p300/CBP-mediated histone acetylation

Wang

Luo

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Glomerulosclerosis and interstitial fibrosis represent the key events in development of diabetic nephropathy (DN), with connective tissue growth factor (CTGF), plasminogen activator inhibitor-1 (PAI-1) and fibronectin 1 (FN-1) playing important roles in these pathogenic processes. To investigate whether the plant metabolite curcumin, which exerts epigenetic modulatory properties when applied as a pharmacologic agent, may prevent DN via inhibition of the JNK pathway and epigenetic histone acetylation, diabetic and age-matched non-diabetic control mice were administered a 3-month course of curcumin analogue (C66), c-Jun N-terminal kinase inhibitor (JNKi, sp600125), or vehicle alone. At treatment end, half of the mice were sacrificed for analysis and the other half were maintained without treatment for an additional 3 months. Renal JNK phosphorylation was found to be significantly increased in the vehicle-treated diabetic mice, but not the C66- and JNKi-treated diabetic mice, at both the 3-month and 6-month time points. C66 and JNKi treatment also significantly prevented diabetes-induced renal fibrosis and dysfunction. Diabetes-related increases in histone acetylation, histone acetyl transferases’ (HATs) activity, and the p300/CBP HAT expression were also significantly attenuated by C66 or JNKi treatment. Chromatin immunoprecipitation assays showed that C66 and JNKi treatments decreased H3-lysine9/14-acetylation (H3K9/14Ac) level and p300/CBP occupancy at the CTGF, PAI-1 and FN-1 gene promoters. Thus, C66 may significantly and persistently prevent renal injury and dysfunction in diabetic mice via down-regulation of diabetes-related JNK activation and consequent suppression of the diabetes-related increases in HAT activity, p300/CBP expression, and histone acetylation.

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Section: Discussionmentioning

confidence: 86%

Novel curcumin analog C66 prevents diabetic nephropathy via JNK pathway with the involvement of p300/CBP-mediated histone acetylation

Wang

Luo

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…HGF produced by osteoblasts induces migration of cancer cells from sinusoidal capillaries to the bone marrow space, where it stimulates growth of cancer cells in the bone microenvironment. HGF induces osteoblasts to enter the cell cycle and to express bone morphogenetic protein 2, which is required for bone formation and repair [Tsai et al 2012]. Thus, osteoblasts appear to promote bone metastasis of some cancers via HGF-MET signaling.…”

Section: Bone Metastasesmentioning

confidence: 99%

Cabozantinib in the treatment of advanced renal cell carcinoma: clinical trial evidence and experience

Ruíz-Morales

Heng

2016

Therapeutic Advances in Urology

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Abstract:The treatment of metastatic renal cell carcinoma (mRCC) is rapidly changing. During first-line treatment with targeted therapy, patients ultimately develop resistance to therapy and the disease progresses. Recently, cabozantinib has demonstrated a better response rate, progression-free survival and overall survival compared with everolimus after failure of prior targeted therapy in patients with advanced or metastatic renal cell carcinoma (RCC). Cabozantinib is a small-molecule tyrosine kinase inhibitor (TKI). It exerts inhibition of MET, vascular endothelial growth factor receptor type 2, AXL, and many other receptor tyrosine kinases that are also implicated in tumor pathobiology, including RET, KIT, and FLT3. MET drives tumor survival, invasion, angiogenesis, and metastasis through several downstream signaling pathways. AXL has recently been described as an essential mediator of cancer metastasis that mediates crosstalk and resistance to TKIs. MET and AXL are thought to be anti-vascular endothelial growth factor receptor (VEGF) resistance pathways and thus cabozantinib represents a logical choice after progression on initial VEGF therapy. Subgroup analyses examining those with good performance status or visceral and bone metastases indicate that the hazard ratios may be better when using cabozantinib versus everolimus. However, there were no clear statistically significant differences between any subgroups.

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“…In contrast, HGF was found to induce the expression of BMP-2 in human osteoblast-like cells, in part by activating Runx2. [73] Autocrine Wnt signaling is necessary to promote BMP-2 induced differentiation in preosteoblasts. [74] Expression of the Wnt inhibitor DKK-1 correlated with lytic bone disease in MM and DKK-1 antagonized BMP induced osteoblast differentiation.…”

Section: Bmp and Bone Disease In Multiple Myelomamentioning

confidence: 99%

The role of bone morphogenetic proteins in myeloma cell survival

Holien

Sundan

2014

Cytokine & Growth Factor Reviews

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Hepatocyte growth factor-induced BMP-2 expression is mediated by c-Met receptor, FAK, JNK, Runx2, and p300 pathways in human osteoblasts

Cited by 33 publications

References 39 publications

Novel curcumin analog C66 prevents diabetic nephropathy via JNK pathway with the involvement of p300/CBP-mediated histone acetylation

Novel curcumin analog C66 prevents diabetic nephropathy via JNK pathway with the involvement of p300/CBP-mediated histone acetylation

Cabozantinib in the treatment of advanced renal cell carcinoma: clinical trial evidence and experience

The role of bone morphogenetic proteins in myeloma cell survival

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