Down-Regulation

Publication Title: 
Circulation

BACKGROUND: C-reactive protein (CRP), the prototypic marker of inflammation, has been shown to be an independent predictor of cardiovascular events. Endothelial nitric oxide synthase (eNOS) deficiency is a pivotal event in atherogenesis. METHODS AND RESULTS: We tested the effect of CRP on eNOS expression and bioactivity in cultured human aortic endothelial cells (HAECs). CRP decreased eNOS mRNA, protein abundance, and enzyme activity in HAECs. Furthermore, eNOS bioactivity assayed by cyclic GMP levels was significantly reduced by CRP.

Author(s): 
Venugopal, Senthil Kumar
Devaraj, Sridevi
Yuhanna, Ivan
Shaul, Philip
Jialal, Ishwarlal
Publication Title: 
The Journal of Biological Chemistry

Osteoblast lineage-specific differentiation of mesenchymal stem cells is a well regulated but poorly understood process. Both bone morphogenetic proteins (BMPs) and Wnt signaling are implicated in regulating osteoblast differentiation and bone formation. Here we analyzed the expression profiles of mesenchymal stem cells stimulated with Wnt3A and osteogenic BMPs, and we identified connective tissue growth factor (CTGF) as a potential target of Wnt and BMP signaling.

Author(s): 
Luo, Qing
Kang, Quan
Si, Weike
Jiang, Wei
Park, Jong Kyung
Peng, Ying
Li, Xinmin
Luu, Hue H.
Luo, Jeffrey
Montag, Anthony G.
Haydon, Rex C.
He, Tong-Chuan
Publication Title: 
Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society

OBJECTIVE: We sought to determine the molecular basis for the anticatabolic effects of mechanical signals on fibrocartilage cells by studying the expression of a variety of matrix metalloproteinases (MMPs). Furthermore, we examined whether the effects of biomechanical strain on MMP gene expression are sustained. METHODS: Fibrochondrocytes from temporomandibular joint (TMJ) discs were exposed to dynamic tensile strain for various time intervals in the presence of interleukin (IL)-1beta.

Author(s): 
Deschner, J.
Rath-Deschner, B.
Agarwal, S.
Publication Title: 
Circulation Research

The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily that is highly expressed in liver, kidney, adrenals, and intestine. FXR may play an important role in the pathogenesis of cardiovascular diseases via regulating the metabolism and transport of cholesterol. In this study, we report that FXR is also expressed in rat pulmonary artery endothelial cells (EC), a "nonclassical" bile acid target tissue.

Author(s): 
He, Fengtian
Li, Jiang
Mu, Ying
Kuruba, Ramalinga
Ma, Zheng
Wilson, Annette
Alber, Sean
Jiang, Yu
Stevens, Troy
Watkins, Simon
Pitt, Bruce
Xie, Wen
Li, Song
Publication Title: 
Molecular Cancer Therapeutics

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor superfamily, which has been shown to preferentially induce apoptosis in cancer cells without adverse effects on normal cells. However, there are still some cancer cells, especially those with high malignancy, resistant to TRAIL-induced apoptosis, impeding the clinical anticancer efficiency of TRAIL.

Author(s): 
Zhang, Siyuan
Shen, Han-Ming
Ong, Choon Nam
Publication Title: 
Journal of Vascular Surgery

BACKGROUND: Homocysteine is an independent risk factor for atherosclerosis. The objective of this study was to investigate whether ginkgolide A (GA), a major constituent of Ginkgo biloba, could block homocysteine-induced endothelial dysfunction in porcine coronary arteries. METHODS: Porcine coronary artery rings were assigned to six treatment groups: control; homocysteine (50 micromol/L); low-dose (50 micromol/L) or high-dose (100 micromol/L) GA; and homocysteine plus low-dose or high-dose GA.

Author(s): 
Zhou, Wei
Chai, Hong
Courson, Andy
Lin, Peter H.
Lumsden, Alan B.
Yao, Qizhi
Chen, Changyi
Publication Title: 
The Journal of Pharmacology and Experimental Therapeutics

Conversion of cholesterol to bile acids in the liver is initiated by the rate-limiting enzyme cholesterol 7alpha-hydroxylase (CYP7A1) and excretion of bile acids from the liver is mediated by the bile salt export pump (BSEP). The expression of CYP7A1 and BSEP is coordinately regulated by a negative feedback and positive feed-forward mechanism, respectively, through bile acid-mediated activation of farsenoid X receptor (FXR). It is well established that hypolipidemic agent guggulsterone is an FXR antagonist and down-regulates FXR target genes.

Author(s): 
Deng, Ruitang
Yang, Dongfang
Radke, Amy
Yang, Jian
Yan, Bingfang
Publication Title: 
Journal of Immunology (Baltimore, Md.: 1950)

In response to inflammatory stimuli (e.g., endotoxin, proinflammatory cytokines) or oxidative stress, macrophages actively release a ubiquitous nuclear protein, high-mobility group box 1 (HMGB1), to sustain an inflammatory response to infection or injury. In this study, we demonstrated mild heat shock (e.g., 42.5 degrees C, 1 h), or enhanced expression of heat shock protein (Hsp) 72 (by gene transfection) similarly rendered macrophages resistant to oxidative stress-induced HMGB1 cytoplasmic translocation and release.

Author(s): 
Tang, Daolin
Kang, Rui
Xiao, Weimin
Jiang, Lei
Liu, Meidong
Shi, Yongzhong
Wang, Kangkai
Wang, Haichao
Xiao, Xianzhong
Publication Title: 
Arthritis and Rheumatism

OBJECTIVE: While the effects of biomechanical signals in the form of joint movement and exercise are known to be beneficial to inflamed joints, limited information is available regarding the intracellular mechanisms of their actions. This study was undertaken to examine the intracellular mechanisms by which biomechanical signals suppress proinflammatory gene induction by the interleukin-1-beta (IL-1beta)-induced NF-kappaB signaling cascade in articular chondrocytes.

Author(s): 
Dossumbekova, Anar
Anghelina, Mirela
Madhavan, Shashi
He, Lingli
Quan, Ning
Knobloch, Thomas
Agarwal, Sudha
Publication Title: 
Human Brain Mapping

The concept that specific acupuncture points have salubrious effects on distant target organ systems is a salient feature of Traditional Chinese Medicine (TCM). In this study, we used a multiple-session experiment to test whether electroacupuncture stimulation at two TCM vision-related acupoints, UB 60 and GB 37, located on the leg, could produce fMRI signal changes in the occipital regions of the brain, and the specificity of this effect when compared with stimulation at an adjacent non-acupoint (NAP). Six normal, acupuncture naive subjects completed the study.

Author(s): 
Kong, Jian
Kaptchuk, Ted J.
Webb, Julia Megan
Kong, Jiang-Ti
Sasaki, Yuka
Polich, Ginger R.
Vangel, Mark G.
Kwong, Kenneth
Rosen, Bruce
Gollub, Randy L.

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