DERMATOLOGY: Targeting blood vessel growth to treat psoriasis
Psoriasis is a common skin disorder that arises when immune cells become overactive and generate unneeded inflammatory responses in the skin. Dysregulated growth of new blood vessels from pre-existing vessels (a process known as angiogenesis) is one hallmark of psoriasis, which is also characterized by thick silvery scales on affected areas of skin and itchy, dry, red patches. A team of researchers, led by Michael Sch?�n, at Georg August University, Germany, has now found that reducing angiogenesis in xenotransplantation models of psoriasis and in mice with a disease that resembles psoriasis alleviates disease. They therefore suggest that their non-viral gene therapy approach to reducing angiogenesis might provide a new approach to treating psoriasis and, perhaps, other inflammatory skin disorders characterized by dysregulated angiogenesis.
TITLE: Halting angiogenesis by non-viral somatic gene therapy alleviates psoriasis and murine psoriasiform skin lesions
VIROLOGY: How hepatitis C virus uses the cells it infects to its own advantage
The current therapy to treat individuals infected with hepatitis C virus (HCV) works in only about half of those treated. Therefore, many individuals remain chronically infected with HCV, something that often leads to liver failure and liver cancer. Research using human liver cell lines, performed by Po-Yuan Ke and Steve Chen, at Academia Sinica, Taiwan, has identified new ways in which HCV coopts normal cellular processes in the cells that it infects to enhance its reproduction and to evade certain aspects of the antiviral immune response. These data not only provide new insight into the ways in which interactions between HCV and the cells it infects can benefit the virus, but also provide potential new avenues of research for the development of novel therapeutic approaches to clearing HCV infection.
TITLE: Activation of the unfolded protein response and autophagy after hepatitis C virus infection suppresses innate antiviral immunity in vitro
PULMONARY: Pinpointing a role for the molecule TGF-beta in lung scarring
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disorder for which there are currently no treatments. It is a progressive disease that results in lung scarring and changes in lung architecture, which together lead to loss of lung function and death. Although the cause(s) of IPF is unclear, dysregulated signaling triggered by the molecule TGF-beta is known to have a role in disease development. Parviz Minoo, Zea Borok, and colleagues, at the University of Southern California, Los Angeles, have now been able to more specifically pinpoint the role of dysregulated TGF-beta signaling in disease development using a mouse model of lung fibrosis (scarring).
The researchers generated mice lacking T-beta-RII – the molecule to which TGF-beta binds to trigger a signaling cascade – on cells lining the lung (epithelial cells). Importantly, these mice showed increased survival and resistance to fibrosis in the chemical-induced model of fibrosis studied. The authors therefore suggest that T-beta-RII could provide a new target for the development of therapeutics to treat IPF.
TITLE: Epithelium-specific deletion of TGF-beta receptor type II protects mice from bleomycin-induced pulmonary fibrosis
MUSCLE BIOLOGY: Linking two previously disparate muscle diseases
Individuals with mutations in their DES gene have dysfunctional muscle fibers in their skeletal and heart muscle (conditions termed myopathy and cardiomyopathy, respectively). This leads to progressive skeletal muscle weakness and heart failure. A team of researchers, led by Jocelyn Laporte, at the Institut de G?�n?�tique et de Biologie Mol?�culaire et Cellulaire, France, has now determined that the mechanisms underlying disease in individuals with a previously unrelated form of inherited myopathy (X-linked centronuclear myopathy [XLCNM]) are similar to those in individuals with DES gene mutations. Specifically, they found that the protein generated by the gene mutated in individuals with XLCNM (MTM1) binds desmin (the product of the DES gene) and ensures normal desmin expression and localization in both both mouse and human skeletal muscles. These and other data in the paper lead the authors to suggest that XLCNM and desmin-related myopathy, two conditions thought previously to be unrelated, have common disease-related features.
TITLE: Myotubularin controls desmin intermediate filament architecture and mitochondrial dynamics in human and mouse skeletal muscle
OPHTHALMOLOGY: Support for light-sensing cells eroded by the mTOR signaling pathway
The retina is the light-sensitive tissue that lines the inner surface of the eye. It consists of light-sensitive nerve cells known as photoreceptors and cells that support and nourish the photoreceptors, which are known as retinal pigment epithelial (RPE) cells. RPE cell dysfunction leads to retinal degeneration and loss of visual acuity. A team of researchers, led by Douglas Vollrath, at Stanford University School of Medicine, Stanford, has now determined in mice that stresses that disrupt the function of the energy generating compartments within RPE cells (mitochondria) trigger RPE cell dedifferentiation and that this leads to decreased responsiveness of photoreceptor cells to light and their eventual degeneration. Further analysis revealed that RPE cell dedifferentiation involved the signaling protein mTOR and that the mTOR inhibitor rapamycin protected photoreceptor function in response to RPE stresses. The authors therefore suggest that mTOR pathway inhibitors might provide a new approach to treating individuals with retinal degenerative diseases involving RPE stress.
TITLE: mTOR-mediated dedifferentiation of the retinal pigment epithelium initiates photoreceptor degeneration in mice
IMMUNOLOGY: Understanding how single immune cells “see” their target
Key to designing effective vaccines and immune-based therapeutics for the treatment of autoimmune diseases such as rheumatoid arthritis is characterizing in detail the immune cells (T cells) that naturally respond to the microbe or cause the autoimmune disease. One facet of this characterization is to define very specifically the protein complex expressed by T cells (the T cell receptor [TCR]) that enables them to “see” their target and respond to microbes or cause autoimmunity. A team of researchers, led by Paul Thomas, at St Jude Children’s Research Hospital, Memphis, has now developed a new method to examine the TCR expressed by an individual T cell, an approach that they hope will prove of tremendous use for researchers studying mouse models of human disease.
TITLE: Paired analysis of TCR-alpha and TCR-beta chains at the single-cell level in mice
Source:
Karen Honey
Journal of Clinical Investigation