Yin and Yang: CCN3 inhibits the pro-fibrotic effects of CCN2

Fibrotic disease is a significant cause of mortality. CCN2 (connective tissue growth factor [CTGF]), a member of the CCN family of matricellular proteins, plays a significant role in driving the fibrogenic effects of cytokines such as transforming growth factor β (TGFβ). It has been proposed that other members of the CCN family can either promote or antagonize the action of CCN2, depending on the context. A recent elegant study published by Bruce Riser and colleagues (Am J Pathol. 174:1725–34, 2009) illustrates that CCN3 (nov) antagonizes the fibrogenic effects of CCN2. This paper, the subject of this commentary, raises the intriguing possibility that CCN3 may be used as a novel anti-fibrotic therapy

Thrombin-induced CCN2 expression as a target for anti-fibrotic therapy in scleroderma

Scleroderma (systemic sclerosis, SSc) is a fibrotic disease for which there is no therapy. CCN2 (connective tissue growth factor, CTGF) is a marker and mediator of fibrosis. Previously, it has been shown that thrombin induces CCN2 expression in fibroblasts. In a recent fascinating report, Bogatkevich et al. (Arthritis Rheum 60:3455–3464, 2009) show that dabigatran, an inhibitor of thrombin action, blocks the overexpression of CCN2 by scleroderma fibroblasts and reverses the contractile phenotype of these cells. These results strongly suggest that dabigatran may be a potential antifibrotic drug for the treatment of fibrosing diseases such as scleroderma

A sticky situation: CCN1 promotes both proliferation and apoptosis of cancer cells

Members of the CCN family of matricellular signaling regulators promote cell adhesion through integrins and heparan sulfate-containing proteoglycans. A paradox of the CCN field is that, depending on the set of circumstances examined, individual CCN molecules can have quite different, and often opposing, effects. In a recent report, Franzen and colleagues (Mol Cancer Res. 7:1045–1055, 2009) show using siRNA knockdown that CCN1 (cyr61) is essential for the proliferation of prostate cancer cells. Intriguingly, on the other hand, CCN1 also enhances TRAIL-induced apoptosis. Thus the utility of anti-CCN1 therapy in cancer needs to be carefully considered in light of these divergent results. The significance of this paper is discussed

Three-centre cluster structure in 11C and 11B

Studies of the 16O(9Be,alpha 7Be)14C, 7Li(9Be,alpha 7Li)5He and 7Li(9Be,alpha alpha t)5He reactions at E(beam)=70 and 55 MeV have been performed using resonant particle spectroscopy techniques. The 11C excited states decaying into alpha+7Be(gs) are observed between 8.5 and 13.5 MeV. The alpha+7Li(gs), alpha+7Li*(4.652 MeV) and t+8Be(gs) decays of 11B excited states between 9 and 19 MeV are observed. The decay processes are used to indicate the possible three-centre 2alpha+3He (2alpha+3H) cluster structure of observed states. This cluster structure is more prominent in the positive-parity states, where two rotational bands with large deformations are suggested. Excitations of some of the observed T=1/2 resonances coincide with the energies of previously measured T=3/2 isobaric analogs of the 11Be states,indicating that these states may have mixed isospin.Comment: Contribution for the proceedings of the NUSTAR'05: NUclear STructure, Astrophysics and Reactions, University of Surrey, Guildford, UK; accepted for publication in Journal of Physics

1/z-renormalization of the mean-field behavior of the dipole-coupled singlet-singlet system HoF_3

The two main characteristics of the holmium ions in HoF_3 are that their local electronic properties are dominated by two singlet states lying well below the remaining 4f-levels, and that the classical dipole-coupling is an order of magnitude larger than any other two-ion interactions between the Ho-moments. This combination makes the system particularly suitable for testing refinements of the mean-field theory. There are four Ho-ions per unit cell and the hyperfine coupled electronic and nuclear moments on the Ho-ions order in a ferrimagnetic structure at T_C=0.53 K. The corrections to the mean-field behavior of holmium triflouride, both in the paramagnetic and ferrimagnetic phase, have been calculated to first order in the high-density 1/z-expansion. The effective medium theory, which includes the effects of the single-site fluctuations, leads to a substantially improved description of the magnetic properties of HoF_3, in comparison with that based on the mean-field approximation.Comment: 26pp, plain-TeX, JJ

Challenges in the Search for Perchlorate and Other Hydrated Minerals With 2.1-μm Absorptions on Mars

A previously unidentified artifact has been found in Compact Reconnaissance Imaging Spectrometer for Mars targeted I/F data. It exists in a small fraction (<0.05%) of pixels within 90% of images investigated and occurs in regions of high spectral/spatial variance. This artifact mimics real mineral absorptions in width and depth and occurs most often at 1.9 and 2.1 μm, thus interfering in the search for some mineral phases, including alunite, kieserite, serpentine, and perchlorate. A filtering step in the data processing pipeline, between radiance and I/F versions of the data, convolves narrow artifacts (“spikes”) with real atmospheric absorptions in these wavelength regions to create spurious absorption-like features. The majority of previous orbital detections of alunite, kieserite, and serpentine we investigated can be confirmed using radiance and raw data, but few to none of the perchlorate detections reported in published literature remain robust over the 1.0- to 2.65-μm wavelength range

Connective tissue growth factor is induced in bleomycin-induced skin scleroderma

The origin of fibrotic cells within connective tissue is unclear. For example, the extent to which microvascular pericytes contribute to the number of myofibroblasts present in dermal fibrosis in uncertain. Connective tissue growth factor (CTGF/CCN2) is a marker and mediator of fibrosis. In this report, we use an antibody recognizing CCN2 to assess the cell types in mouse dermis which express CCN2 in the bleomycin model of skin scleroderma. Control (PBS injected) and fibrotic (bleomycin-injected) dermis was examined for CCN2, α-smooth muscle actin (α-SMA) (to detect myofibroblasts), and NG2 (to detect pericytes) expression. Consistent with previously published data, CCN2 expression was largely absent in the dermis of control mice. However, upon exposure to bleomycin, CCN2 was observed in the dermis. Cells that expressed CCN2 were α−SMA-expressing myofibroblasts. Approximately 85% of myofibroblasts were NG2-positive, CCN2-expressing pericytes, indicating that pericytes significantly contributed to the presence of myofibroblasts in sclerotic dermis. Thus CCN2 is induced in fibrotic skin, correlating with the induction of myofibroblast induction. Moreover, CCN2-expressing pericytes significantly contribute to the appearance of myofibroblasts in bleomycin-induced skin scleroderma