@article{BingShiTanKressCastroetal.2013,
  author    = {Bing-Shi Tan, Ariel and Kress, Sebastian and Castro, Leticia and Sheppard, Allan and Raghunath, Michael},
  title     = {Cellular re- and de-programming by microenvironmental memory: why short TGF-β1 pulses can have long effects},
  series = {Fibrogenesis Tissue Repair},
  volume    = {6},
  journal   = {Fibrogenesis Tissue Repair},
  number    = {12},
  doi       = {10.1186/1755-1536-6-12},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131898},
  year      = {2013},
  abstract  = {Background Fibrosis poses a substantial setback in regenerative medicine. Histopathologically, fibrosis is an excessive accumulation of collagen affected by myofibroblasts and this can occur in any tissue that is exposed to chronic injury or insult. Transforming growth factor (TGF)-β1, a crucial mediator of fibrosis, drives differentiation of fibroblasts into myofibroblasts. These cells exhibit α-smooth muscle actin (α-SMA) and synthesize high amounts of collagen I, the major extracellular matrix (ECM) component of fibrosis. While hormones stimulate cells in a pulsatile manner, little is known about cellular response kinetics upon growth factor impact. We therefore studied the effects of short TGF-β1 pulses in terms of the induction and maintenance of the myofibroblast phenotype. Results Twenty-four hours after a single 30 min TGF-β1 pulse, transcription of fibrogenic genes was upregulated, but subsided 7 days later. In parallel, collagen I secretion rate and α-SMA presence were elevated for 7 days. A second pulse 24 h later extended the duration of effects to 14 days. We could not establish epigenetic changes on fibrogenic target genes to explain the long-lasting effects. However, ECM deposited under singly pulsed TGF-β1 was able to induce myofibroblast features in previously untreated fibroblasts. Dependent on the age of the ECM (1 day versus 7 days' formation time), this property was diminished. Vice versa, myofibroblasts were cultured on fibroblast ECM and cells observed to express reduced (in comparison with myofibroblasts) levels of collagen I. Conclusions We demonstrated that short TGF-β1 pulses can exert long-lasting effects on fibroblasts by changing their microenvironment, thus leaving an imprint and creating a reciprocal feed-back loop. Therefore, the ECM might act as mid-term memory for pathobiochemical events. We would expect this microenvironmental memory to be dependent on matrix turnover and, as such, to be erasable. Our findings contribute to the current understanding of fibroblast induction and maintenance, and have bearing on the development of antifibrotic drugs.},
  language  = {en}
}
@article{HartliebKempfPartillaetal.2013,
  author    = {Hartlieb, Eva and Kempf, Bettina and Partilla, Miriam and Vigh, Bal{\´a}zs and Spindler, Volker and Waschke, Jens},
  title     = {Desmoglein 2 Is Less Important than Desmoglein 3 for Keratinocyte Cohesion},
  series = {PLoS ONE},
  volume    = {8},
  journal   = {PLoS ONE},
  number    = {1},
  doi       = {10.1371/journal.pone.0053739},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131192},
  pages     = {e53739},
  year      = {2013},
  abstract  = {Desmosomes provide intercellular adhesive strength required for integrity of epithelial and some non-epithelial tissues. Within the epidermis, the cadherin-type adhesion molecules desmoglein (Dsg) 1-4 and desmocollin (Dsc) 1-3 build the adhesive core of desmosomes. In keratinocytes, several isoforms of these proteins are co-expressed. However, the contribution of specific isoforms to overall cell cohesion is unclear. Therefore, in this study we investigated the roles of Dsg2 and Dsg3, the latter of which is known to be essential for keratinocyte adhesion based on its autoantibody-induced loss of function in the autoimmune blistering skin disease pemphigus vulgaris (PV). The pathogenic PV antibody AK23, targeting the Dsg3 adhesive domain, led to profound loss of cell cohesion in human keratinocytes as revealed by the dispase-based dissociation assays. In contrast, an antibody against Dsg2 had no effect on cell cohesion although the Dsg2 antibody was demonstrated to interfere with Dsg2 transinteraction by single molecule atomic force microscopy and was effective to reduce cell cohesion in intestinal epithelial Caco-2 cells which express Dsg2 as the only Dsg isoform. To substantiate these findings, siRNA-mediated silencing of Dsg2 or Dsg3 was performed in keratinocytes. In contrast to Dsg3-depleted cells, Dsg2 knockdown reduced cell cohesion only under conditions of increased shear. These experiments indicate that specific desmosomal cadherins contribute differently to keratinocyte cohesion and that Dsg2 compared to Dsg3 is less important in this context.},
  language  = {en}
}
@article{SchreiberSchneideratKressetal.2013,
  author    = {Schreiber, Olivia and Schneiderat, Peter and Kress, Wolfram and Rautenstrauss, Bernd and Senderek, Jan and Schoser, Bendikt and Walter, Maggie C.},
  title     = {Facioscapulohumeral muscular dystrophy and Charcot-Marie-Tooth neuropathy 1A-evidence for "double trouble" overlapping syndromes},
  series = {BMC Medical Genetics},
  volume    = {14},
  journal   = {BMC Medical Genetics},
  number    = {92},
  issn      = {1471-2350},
  doi       = {10.1186/1471-2350-14-92},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121963},
  year      = {2013},
  abstract  = {Background: We report on a patient with genetically confirmed overlapping diagnoses of CMT1A and FSHD. This case adds to the increasing number of unique patients presenting with atypical phenotypes, particularly in FSHD. Even if a mutation in one disease gene has been found, further genetic testing might be warranted in cases with unusual clinical presentation. Case presentation: The reported 53 years old male patient suffered from walking difficulties and foot deformities first noticed at age 20. Later on, he developed scapuloperoneal and truncal muscle weakness, along with atrophy of the intrinsic hand and foot muscles, pes cavus, claw toes and a distal symmetric hypoesthesia. Motor nerve conduction velocities were reduced to 20 m/s in the upper extremities, and not educible in the lower extremities, sensory nerve conduction velocities were not attainable. Electromyography showed both, myopathic and neurogenic changes. A muscle biopsy taken from the tibialis anterior muscle showed a mild myopathy with some neurogenic findings and hypertrophic type 1 fibers. Whole-body muscle MRI revealed severe changes in the lower leg muscles, tibialis anterior and gastrocnemius muscles were highly replaced by fatty tissue. Additionally, fatty degeneration of shoulder girdle and straight back muscles, and atrophy of dorsal upper leg muscles were seen. Taken together, the presenting features suggested both, a neuropathy and a myopathy. Patient's family history suggested an autosomal dominant inheritance. Molecular testing revealed both, a hereditary motor and sensory neuropathy type 1A (HMSN1A, also called Charcot-Marie-Tooth neuropathy 1A, CMT1A) due to a PMP22 gene duplication and facioscapulohumeral muscular dystrophy (FSHD) due to a partial deletion of the D4Z4 locus (19 kb). Conclusion: Molecular testing in hereditary neuromuscular disorders has led to the identification of an increasing number of atypical phenotypes. Nevertheless, finding the right diagnosis is crucial for the patient in order to obtain adequate medical care and appropriate genetic counseling, especially in the background of arising curative therapies.},
  language  = {en}
}