Connective tissue growth factor (CTGF, CCN2) gene regulation: a potent clinical bio-marker of fibroproliferative disease?

The CCN (cyr61, ctgf, nov) family of modular proteins regulate diverse biological affects including cell adhesion, matrix production, tissue remodelling, proliferation and differentiation. Recent targeted gene disruption studies have demonstrated the CCN family to be developmentally essential for chondrogenesis, osteogenesis and angiogenesis. CCN2 is induced by agents such as angiotensin II, endothelin-1, glucocorticoids, HGF, TGFβ, and VEGF, and by hypoxia and biomechanical and shear stress. Dysregulated expression of CCN2 has also been widely documented in many fibroproliferative diseases. This mini-review will focus on CCN2, and the recent progress in understanding CCN2 gene regulation in health and disease. That CCN2 should be considered a novel and informative surrogate clinical bio-marker for fibroproliferative disease is discussed

Distinct Signature of Altered Homeostasis in Aging Rod Photoreceptors: Implications for Retinal Diseases

Advanced age contributes to clinical manifestations of many retinopathies and represents a major risk factor for age-related macular degeneration, a leading cause of visual impairment and blindness in the elderly. Rod photoreceptors are especially vulnerable to genetic defects and changes in microenvironment, and are among the first neurons to die in normal aging and in many retinal degenerative diseases. The molecular mechanisms underlying rod photoreceptor vulnerability and potential biomarkers of the aging process in this highly specialized cell type are unknown.To discover aging-associated adaptations that may influence rod function, we have generated gene expression profiles of purified rod photoreceptors from mouse retina at young adult to early stages of aging (1.5, 5, and 12 month old mice). We identified 375 genes that showed differential expression in rods from 5 and 12 month old mouse retina compared to that of 1.5 month old retina. Quantitative RT-PCR experiments validated expression change for a majority of the 25 genes that were examined. Macroanalysis of differentially expressed genes using gene class testing and protein interaction networks revealed overrepresentation of cellular pathways that are potentially photoreceptor-specific (angiogenesis and lipid/retinoid metabolism), in addition to age-related pathways previously described in several tissue types (oxidative phosphorylation, stress and immune response).Our study suggests a progressive shift in cellular homeostasis that may underlie aging-associated functional decline in rod photoreceptors and contribute to a more permissive state for pathological processes involved in retinal diseases

Retinitis Pigmentosa GTPase Regulator (RPGR) protein isoforms in mammalian retina:insights into X-linked Retinitis Pigmentosa and associated ciliopathies

AbstractMutations in the cilia-centrosomal protein Retinitis Pigmentosa GTPase Regulator (RPGR) are a frequent cause of retinal degeneration. The RPGR gene undergoes complex alternative splicing and encodes multiple protein isoforms. To elucidate the function of major RPGR isoforms (RPGR1–19 and RPGRORF15), we have generated isoform-specific antibodies and examined their expression and localization in the retina. Using sucrose-gradient centrifugation, immunofluorescence and co-immunoprecipitation methods, we show that RPGR isoforms localize to distinct sub-cellular compartments in mammalian photoreceptors and associate with a number of cilia-centrosomal proteins. The RCC1-like domain of RPGR, which is present in all major RPGR isoforms, is sufficient to target it to the cilia and centrosomes in cultured cells. Our findings indicate that multiple isotypes of RPGR may perform overlapping yet somewhat distinct transport-related functions in photoreceptors

Expression of heme oxygenase-1 mRNA in vitreous-treated retinal pigment epithelial cells

Low passage donor retinal pigment epithelial (RPE) cells were incubated with or without vitreous for up to 24 h. RNA was extracted at each time point and heme oxygenase-1 (HO-1) mRNA was measured by qPCR. Ribosomal protein, large, P0 (RPLP0) was used as an internal standard to correct for small differences in the amount of cDNA used in each reaction. Each point at a particular time indicates a different RPE/vitreous donor pair. The number of donor/vitreous pairs examined at each time point is shown. At 6, 12, and 24 h, REST-XL analysis indicated that HO-1 mRNA was significantly increased (p<p><b>Copyright information:</b></p><p>Taken from "Vitreous induces heme oxygenase-1 expression mediated by transforming growth factor-β and reactive oxygen species generation in human retinal pigment epithelial cells"</p><p></p><p>Molecular Vision 2007;13():66-78.</p><p>Published online 24 Jan 2007</p><p>PMCID:PMC2503184.</p><p></p