Journal of Clinical Investigation -- Current IssueJournal of Clinical Investigation RSS feed -- Current issueLipid droplets: FSP27 knockout enhances their sizzle- (Found August 15, 2008 ) Fat-specific protein of 27 kDa (FSP27) is a highly expressed adipocyte protein that promotes triglyceride accumulation within lipid droplets. In this issue of the JCI, Nishino et al. show that FSP27 also helps to maintain the characteristically large unilocular lipid droplet structure within each white adipocyte (see the related article beginning on page 2808). Fragmentation of lipid droplets in white adipocytes from FSP27-KO mice caused both increased lipolysis and upregulation of genes...http://www.jci.org/articles/view/36554 Androgen receptor-negative human prostate cancer cells induce osteogenesis in mice through FGF9-mediated mechanisms- (Found August 15, 2008 ) In prostate cancer, androgen blockade strategies are commonly used to treat osteoblastic bone metastases. However, responses to these therapies are typically brief, and the mechanism underlying androgen-independent progression is not clear. Here, we established what we believe to be the first human androgen receptor&x02013;negative prostate cancer xenografts whose cells induced an osteoblastic reaction in bone and in the subcutis of immunodeficient mice. Accordingly, these cells grew in...http://www.jci.org/articles/view/33093 KLF6-SV1 overexpression accelerates human and mouse prostate cancer progression and metastasis- (Found August 15, 2008 ) Metastatic prostate cancer (PCa) is one of the leading causes of death from cancer in men. The molecular mechanisms underlying the transition from localized tumor to hormone-refractory metastatic PCa remain largely unknown, and their identification is key for predicting prognosis and targeted therapy. Here we demonstrated that increased expression of a splice variant of the Kruppel-like factor 6 (KLF6) tumor suppressor gene, known as KLF6-SV1, in tumors from men after prostatectomy predicted...http://www.jci.org/articles/view/34780 Keratinocyte-specific Smad2 ablation results in increased epithelial-mesenchymal transition during skin cancer formation and progression- (Found August 15, 2008 ) TGF-&x003b2; and its signaling mediators, Smad2, -3, and -4, are involved with tumor suppression and promotion functions. Smad4&x02013;&x02013; mouse epidermis develops spontaneous skin squamous cell carcinomas (SCCs), and Smad3&x02013;&x02013; mice are resistant to carcinogen-induced skin cancer; however, the role of Smad2 in skin carcinogenesis has not been explored. In the present study, we found that Smad2 and Smad4, but not Smad3, were frequently lost in human SCCs. Mice with...http://www.jci.org/articles/view/33713 Ang II-stimulated migration of vascular smooth muscle cells is dependent on LR11 in mice- (Found August 15, 2008 ) Medial-to-intimal migration of SMCs is critical to atherosclerotic plaque formation and remodeling of injured arteries. Considerable amounts of the shed soluble form of the LDL receptor relative LR11 (sLR11) produced by intimal SMCs enhance SMC migration in vitro via upregulation of urokinase-type plasminogen activator receptor (uPAR) expression. Here, we show that circulating sLR11 is a novel marker of carotid intima-media thickness (IMT) and that targeted disruption of the LR11 gene greatly...http://www.jci.org/articles/view/32381 Multidrug resistance-associated protein 4 regulates cAMP-dependent signaling pathways and controls human and rat SMC proliferation- (Found August 15, 2008 ) The second messengers cAMP and cGMP can be degraded by specific members of the phosphodiesterase superfamily or by active efflux transporters, namely the multidrug resistance-associated proteins (MRPs) MRP4 and MRP5. To determine the role of MRP4 and MRP5 in cell signaling, we studied arterial SMCs, in which the effects of cyclic nucleotide levels on SMC proliferation have been well established. We found that MRP4, but not MRP5, was upregulated during proliferation of isolated human coronary...http://www.jci.org/articles/view/35067 Coxsackievirus and adenovirus receptor (CAR) mediates atrioventricular-node function and connexin 45 localization in the murine heart- (Found August 15, 2008 ) The coxsackievirus and adenovirus receptor (CAR) is a transmembrane protein that belongs to the family of adhesion molecules. In the postnatal heart, it is localized predominantly at the intercalated disc, where its function is not known. Here, we demonstrate that a first degree or complete block of atrioventricular (AV) conduction developed in the absence of CAR in the adult mouse heart and that prolongation of AV conduction occurred in the embryonic heart of the global CAR-KO mouse. In the...http://www.jci.org/articles/view/34777 Cigarette smoke selectively enhances viral PAMP- and virus-induced pulmonary innate immune and remodeling responses in mice- (Found August 15, 2008 ) Viral infections have more severe consequences in patients who have been exposed to cigarette smoke (CS) than in those not exposed to CS. For example, in chronic obstructive pulmonary disease (COPD), viruses cause more severe disease exacerbation, heightened inflammation, and accelerated loss of lung function compared with other causes of disease exacerbation. Symptomatology and mortality in influenza-infected smokers is also enhanced. To test the hypothesis that these outcomes are caused by...http://www.jci.org/articles/view/32709 Phosphorylation of GSK-3beta by cGMP-dependent protein kinase II promotes hypertrophic differentiation of murine chondrocytes- (Found August 15, 2008 )http://www.jci.org/articles/view/35243E1 |