@article{SaudekCahovaHavrdovaetal.2018,
  author    = {Saudek, František and Cahov{\´a}, Monika and Havrdov{\´a}, Terezie and Zacharovov{\´a}, Kl{\´a}ra and Daňkov{\´a}, Helena and Voska, Luděk and L{\´a}nsk{\´a}, Věra and {\"U}{\c{c}}eyler, Nurcan and Sommer, Claudia},
  title     = {Preserved Expression of Skin Neurotrophic Factors in Advanced Diabetic Neuropathy Does Not Lead to Neural Regeneration despite Pancreas and Kidney Transplantation},
  series = {Journal of Diabetes Research},
  volume    = {2018},
  journal   = {Journal of Diabetes Research},
  number    = {2309108},
  doi       = {10.1155/2018/2309108},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227469},
  pages     = {1-11},
  year      = {2018},
  abstract  = {Diabetic peripheral neuropathy (DPN) is a common complication of diabetes with potential severe consequences. Its pathogenesis involves hyperglycemia-linked mechanisms, which may include changes in the expression of neurotrophic growth factors. We analyzed the expression of 29 factors potentially related to nerve degeneration and regeneration in skin biopsies from 13 type 1 diabetic pancreas and kidney recipients with severe DPN including severe depletion of intraepidermal nerve fibers (IENF) in lower limb skin biopsies (group Tx1 1st examination). The investigation was repeated after a median 28-month period of normoglycemia achieved by pancreas transplantation (group Tx1 2nd examination). The same tests were performed in 13 stable normoglycemic pancreas and kidney recipients 6-12 years posttransplantation (group Tx2), in 12 matched healthy controls (group HC), and in 12 type 1 diabetic subjects without severe DPN (group DM). Compared to DM and HC groups, we found a significantly higher (p < 0.05-0.001) expression of NGF (nerve growth factor), NGFR (NGF receptor), NTRK1 (neurotrophic receptor tyrosine kinase 1), GDNF (glial cell-derived neurotrophic factor), GFRA1 (GDNF family receptor alpha 1), and GFAP (glial fibrillary acidic protein) in both transplant groups (Tx1 and Tx2). Enhanced expression of these factors was not normalized following the median 28-month period of normoglycemia (Tx1 2nd examination) and negatively correlated with IENF density and with electrophysiological indices of DPN (vibration perception threshold, electromyography, and autonomic tests). In contrast to our expectation, the expression of most of 29 selected factors related to neural regeneration was comparable in subjects with severe peripheral nerve fiber depletion and healthy controls and the expression of six factors was significantly upregulated. These findings may be important for better understanding the pathophysiology of nerve regeneration and for the development of intervention strategies.},
  language  = {en}
}
@article{RegnLaggerbauerJentzschetal.2016,
  author    = {Regn, Michael and Laggerbauer, Bernhard and Jentzsch, Claudia and Ramanujam, Deepak and Ahles, Andrea and Sichler, Sonja and Calzada-Wack, Julia and Koenen, Rory R. and Braun, Attila and Nieswandt, Bernhard and Engelhardt, Stefan},
  title     = {Peptidase inhibitor 16 is a membrane-tethered regulator of chemerin processing in the myocardium},
  series = {Journal of Molecular and Cellular Cardiology},
  volume    = {99},
  journal   = {Journal of Molecular and Cellular Cardiology},
  doi       = {10.1016/j.yjmcc.2016.08.010},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187039},
  pages     = {57-64},
  year      = {2016},
  abstract  = {A key response of the myocardium to stress is the secretion of factors with paracrine or endocrine function. Intriguing in this respect is peptidase inhibitor 16 (PI16), a member of the CAP family of proteins which we found to be highly upregulated in cardiac disease. Up to this point, the mechanism of action and physiological function of PI16 remained elusive. Here, we show that PI16 is predominantly expressed by cardiac fibroblasts, which expose PI16 to the interstitium via a glycophosphatidylinositol (-GPI) membrane anchor. Based on a reported genetic association of PI16 and plasma levels of the chemokine chemerin, we investigated whether PI16 regulates post-translational processing of its precursor pro-chemerin. PI16-deficient mice were engineered and found to generate higher levels of processed chemerin than wildtype mice. Purified recombinant PI16 efficiently inhibited cathepsin K, a chemerin-activating protease, in vitro. Moreover, we show that conditioned medium from PI16-overexpressing cells impaired the activation of pro-chemerin. Together, our data indicate that PI16 suppresses chemerin activation in the myocardium and suggest that this circuit may be part of the cardiac stress response.},
  language  = {en}
}