@inproceedings{ChenReichetzederFoelleretal.2015,
  author    = {Chen, Hong and Reichetzeder, Christoph and F{\"o}ller, Michael and Slowinski, Torsten and Li, Jian and Chen, You-Peng and Lang, Florian and Hocher, Berthold},
  title     = {Maternal vitamin D deficiency and fetal programming},
  series = {Acta physiologica : official journal of the Federation of European Physiological Societies},
  volume    = {213},
  booktitle = {Acta physiologica : official journal of the Federation of European Physiological Societies},
  publisher = {Wiley-Blackwell},
  address   = {Hoboken},
  issn      = {1748-1708},
  pages     = {155 -- 156},
  year      = {2015},
  language  = {en}
}
@article{DschietzigKrauseRelleHennequinetal.2015,
  author    = {Dschietzig, Thomas Bernd and Krause-Relle, Katharina and Hennequin, Maud and von Websky, Karoline and Rahnenfuhrer, Jan and Ruppert, Jana and Groena, Hans Juergen and Armbruster, Franz Paul and Bathgate, Ross A. D. and Aschenbach, Joerg R. and Forssmann, Wolf-Georg and Hocher, Berthold},
  title     = {Relaxin-2 does not Ameliorate Nephropathy in an experimental model of Type-1 Diabetes},
  series = {Kidney \& blood pressure research : official organ of the Gesellschaft f{\"u}r Nephrologie},
  volume    = {40},
  journal   = {Kidney \& blood pressure research : official organ of the Gesellschaft f{\"u}r Nephrologie},
  number    = {1},
  publisher = {Karger},
  address   = {Basel},
  issn      = {1420-4096},
  doi       = {10.1159/000368484},
  pages     = {77 -- 88},
  year      = {2015},
  abstract  = {Background/Aims: In diabetic nephropathy (DN), the current angiotensin-II-blocking pharmacotherapy is frequently failing. For diabetic cardiomyopathy (DC), there is no specific remedy available. Relaxin-2 (Rlx) - an anti-fibrotic, anti-inflammatory, and vasoprotecting peptide - is a candidate drug for both. Methods: Low-dose (32 mu g/kg/day) and high-dose (320 mu g/kg/day) Rlx were tested against vehicle (n = 20 each) and non-diabetic controls (n = 14) for 12 weeks in a model of type-1 diabetes induced in endothelial nitric oxide synthase knock-out (eNOS-KO) mice by intraperitoneal injection of streptozotocin. Results: Diabetic animals showed normal plasma creatinine, markedly increased albuminuria and urinary malonyldialdehyde, elevated relative kidney weight, glomerulosclerosis, and increased glomerular size, but no relevant interstitial fibrosis. Neither dose of Rlx affected these changes although the drug was active and targeted plasma levels were achieved. Of note, we found no activation of the renal TGF-beta pathway in this model. In the hearts of diabetic animals, no fibrotic alterations indicative of DC could be determined which precluded testing of the initial hypothesis. Conclusions: We investigated a model showing early DN without overt tubulo-interstitial fibrosis and activation of the TGF-beta-Smad-2/3 pathway. In this model, Rlx proved ineffective; however, the same may not apply to other models and types of diabetes.},
  language  = {en}
}
@article{GroopCooperPerkovicetal.2015,
  author    = {Groop, Per-Henrik and Cooper, Mark E. and Perkovic, Vlado and Sharma, Kumar and Schernthaner, Guntram and Haneda, Masakazu and Hocher, Berthold and Gordat, Maud and Cescutti, Jessica and Woerle, Hans-Juergen and von Eynatten, Maximilian},
  title     = {Dipeptidyl peptidase-4 inhibition with linagliptin and effects on hyperglycaemia and albuminuria in patients with type 2 diabetes and renal dysfunction: Rationale and design of the MARLINA-T2D trial},
  series = {Diabetes \& vascular disease research : official journal of the International Society of Diabetes and Vascular Disease},
  volume    = {12},
  journal   = {Diabetes \& vascular disease research : official journal of the International Society of Diabetes and Vascular Disease},
  number    = {6},
  publisher = {Sage Publ.},
  address   = {London},
  issn      = {1479-1641},
  doi       = {10.1177/1479164115579002},
  pages     = {455 -- 462},
  year      = {2015},
  abstract  = {Efficacy, Safety \& Modification of Albuminuria in Type 2 Diabetes Subjects with Renal Disease with LINAgliptin (MARLINA-T2D), a multicentre, multinational, randomized, double-blind, placebo-controlled, parallel-group, phase 3b clinical trial, aims to further define the potential renal effects of dipeptidyl peptidase-4 inhibition beyond glycaemic control. A total of 350 eligible individuals with inadequately controlled type 2 diabetes and evidence of renal disease are planned to be randomized in a 1:1 ratio to receive either linagliptin 5mg or placebo in addition to their stable glucose-lowering background therapy for 24weeks. Two predefined main endpoints will be tested in a hierarchical manner: (1) change from baseline in glycated haemoglobin and (2) time-weighted average of percentage change from baseline in urinary albumin-to-creatinine ratio. Both endpoints are sufficiently powered to test for superiority versus placebo after 24weeks with =0.05. MARLINA-T2D is the first of its class to prospectively explore both the glucose- and albuminuria-lowering potential of a dipeptidyl peptidase-4 inhibitor in patients with type 2 diabetes and evidence of renal disease.},
  language  = {en}
}
@misc{GroopCooperPerkovicetal.2015,
  author    = {Groop, Per-Henrik and Cooper, Mark E. and Perkovic, Vlado and Sharma, Kumar and Schernthaner, Guntram and Haneda, Masakazu and Hocher, Berthold and Gordat, Maud and Cescutti, Jessica and Woerle, Hans-Juergen and von Eynatten, Maximilian},
  title     = {Dipeptidyl peptidase-4 inhibition with linagliptin and effects on hyperglycaemia and albuminuria in patients with type 2 diabetes and renal dysfunction},
  series = {Diabetes \& vascular disease research},
  journal   = {Diabetes \& vascular disease research},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-404460},
  pages     = {8},
  year      = {2015},
  abstract  = {Efficacy, Safety \& Modification of Albuminuria in Type 2 Diabetes Subjects with Renal Disease with LINAgliptin (MARLINA-T2D), a multicentre, multinational, randomized, double-blind, placebo-controlled, parallel-group, phase 3b clinical trial, aims to further define the potential renal effects of dipeptidyl peptidase-4 inhibition beyond glycaemic control. A total of 350 eligible individuals with inadequately controlled type 2 diabetes and evidence of renal disease are planned to be randomized in a 1:1 ratio to receive either linagliptin 5mg or placebo in addition to their stable glucose-lowering background therapy for 24weeks. Two predefined main endpoints will be tested in a hierarchical manner: (1) change from baseline in glycated haemoglobin and (2) time-weighted average of percentage change from baseline in urinary albumin-to-creatinine ratio. Both endpoints are sufficiently powered to test for superiority versus placebo after 24weeks with =0.05. MARLINA-T2D is the first of its class to prospectively explore both the glucose- and albuminuria-lowering potential of a dipeptidyl peptidase-4 inhibitor in patients with type 2 diabetes and evidence of renal disease.},
  language  = {en}
}
@misc{HoffmannKretschmerLawrenzetal.2015,
  author    = {Hoffmann, Linda Sarah and Kretschmer, Axel and Lawrenz, Bettina and Hocher, Berthold and Stasch, Johannes-Peter},
  title     = {Chronic activation of heme free Guanylate Cyclase leads to renal protection in Dahl salt-sensitive rats},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch naturwissenschaftliche Reihe},
  number    = {489},
  issn      = {1866-8372},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-408088},
  pages     = {17},
  year      = {2015},
  abstract  = {The nitric oxide (NO)/soluble guanylate cyclase (sGC)/cyclic guanosine monophasphate (cGMP)-signalling pathway is impaired under oxidative stress conditions due to oxidation and subsequent loss of the prosthetic sGC heme group as observed in particular in chronic renal failure. Thus, the pool of heme free sGC is increased under pathological conditions. sGC activators such as cinaciguat selectively activate the heme free form of sGC and target the disease associated enzyme. In this study, a therapeutic effect of long-term activation of heme free sGC by the sGC activator cinaciguat was investigated in an experimental model of salt-sensitive hypertension, a condition that is associated with increased oxidative stress, heme loss from sGC and development of chronic renal failure. For that purpose Dahl/ss rats, which develop severe hypertension upon high salt intake, were fed a high salt diet (8\% NaCl) containing either placebo or cinaciguat for 21 weeks. Cinaciguat markedly improved survival and ameliorated the salt-induced increase in blood pressure upon treatment with cinaciguat compared to placebo. Renal function was significantly improved in the cinaciguat group compared to the placebo group as indicated by a significantly improved glomerular filtration rate and reduced urinary protein excretion. This was due to anti-fibrotic and antiinflammatory effects of the cinaciguat treatment. Taken together, this is the first study showing that long-term activation of heme free sGC leads to renal protection in an experimental model of hypertension and chronic kidney disease. These results underline the promising potential of cinaciguat to treat renal diseases by targeting the disease associated heme free form of sGC.},
  language  = {en}
}
@misc{OngvonWebskyHocher2015,
  author    = {Ong, Albert C. M. and von Websky, Karoline and Hocher, Berthold},
  title     = {Endothelin and Tubulointerstitial Renal Disease},
  series = {Seminars in nephrology},
  volume    = {35},
  journal   = {Seminars in nephrology},
  number    = {2},
  publisher = {Elsevier},
  address   = {Philadelphia},
  issn      = {0270-9295},
  doi       = {10.1016/j.semnephrol.2015.03.004},
  pages     = {197 -- 207},
  year      = {2015},
  abstract  = {All components of the endothelin (ET) system are present in renal tubular cells. In this review, we summarize current knowledge about ET and the most common tubular diseases: acute kidney injury (AKI) and polycystic kidney disease. AKI originally was called acute tubular necrosis, pointing to the most prominent morphologic findings. Similarly, cysts in polycystic kidney disease, and especially in autosomal-dominant polycystic kidney disease, are of tubular origin. Preclinical studies have indicated that the ET system and particularly ETA receptors are involved in the pathogenesis of ischemia-reperfusion injury, although these findings have not been translated to clinical studies. The ET system also has been implicated in radiocontrast-dye-induced AKI, however, ET-receptor blockade in a large human study was not successful. The ET system is activated in sepsis models of AKI; the effectiveness of ET blocking agents in preclinical studies is variable depending on the model and the ET-receptor antagonist used. Numerous studies have shown that the ET system plays an important role in the complex pathophysiology associated with cyst formation and disease progression in polycystic kidney disease. However, results from selective targeting of ET-receptor subtypes in animal models of polycystic kidney disease have proved disappointing and do not support clinical trials. These studies have shown that a critical balance between ETA and ETB receptor action is necessary to maintain structure and function in the cystic kidney. In summary, ETs have been implicated in the pathogenesis of several renal tubulointerstitial diseases, however, experimental animal findings have not yet led to use of ET blockers in human beings. (C) 2015 Elsevier Inc. All rights reserved.},
  language  = {en}
}
@article{PengZhuDongetal.2015,
  author    = {Peng, Tao and Zhu, Ganghua and Dong, Yunpeng and Zeng, Junjie and Li, Wei and Guo, Weiwei and Chen, Yong and Duan, Maoli and Hocher, Berthold and Xie, Dinghua},
  title     = {BMP4: a possible key factor in differentiation of auditory neuron-like cells from bone-derived mesenchymal stromal cells},
  series = {Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion},
  volume    = {61},
  journal   = {Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion},
  number    = {9},
  publisher = {Clin Lab Publ., Verl. Klinisches Labor},
  address   = {Heidelberg},
  issn      = {1433-6510},
  doi       = {10.7754/Clin.Lab.2015.150217},
  pages     = {1171 -- 1178},
  year      = {2015},
  abstract  = {Background: Previous studies have shown that BMP4 may play an important part in the development of auditory neurons (ANs), which are degenerated in sensorineural hearing loss. However, whether BMP4 can promote sensory fate specification from mesenchymal stromal cells (MSCs) is unknown so far. Methods: MSCs isolated from Sprague-Dawley (SD) rats were confirmed by expression of MSC markers using flow cytometry and adipogenesis/osteogenesis using differentiation assays. MSCs treated with a complex of neurotrophic factors (BMP4 group and non-BMP4 group) were induced into auditory neuron-like cells, then the differences between the two groups were analyzed in morphological observation, cell growth curve, qRT-PCR, and immunofluorescence. Results: Flow cytometric analysis showed that the isolated cells expressed typical MSC surface markers. After adipogenic and osteogenic induction, the cells were stained by oil red O and Alizarin Red. The neuronal induced cells were in the growth plateau and had special forms of neurons. In the presence of BMP4, the inner ear genes NF-M, Neurog1, GluR4, NeuroD, Calretinin, NeuN, Tau, and GATA3 were up-regulated in MSCs. Conclusions: MSCs have the capacity to differentiate into auditory neuron-like cells in vitro. As an effective inducer, BMP4 may play a key role in transdifferentiation.},
  language  = {en}
}
@inproceedings{ReichetzedervonWebskyTsuprykovetal.2015,
  author    = {Reichetzeder, Christoph and von Websky, Karoline and Tsuprykov, Oleg and Antonenko, V. and Samarin, Azin Mohagheghi and Hocher, Berthold},
  title     = {Effects of DPP-4 inhibition on glomerular and tubular function in a rat model of ischaemia-reperfusion injury},
  series = {Diabetologia : journal of the European Association for the Study of Diabetes (EASD)},
  volume    = {58},
  booktitle = {Diabetologia : journal of the European Association for the Study of Diabetes (EASD)},
  publisher = {Springer},
  address   = {New York},
  issn      = {0012-186X},
  pages     = {S34 -- S35},
  year      = {2015},
  language  = {en}
}
@article{SatwikoIkedaNakayamaetal.2015,
  author    = {Satwiko, Muhammad Gahan and Ikeda, Koji and Nakayama, Kazuhiko and Yagi, Keiko and Hocher, Berthold and Hirata, Ken-Ichi and Emoto, Noriaki},
  title     = {Targeted activation of endothelin-1 exacerbates hypoxia-induced pulmonary hypertension},
  series = {Biochemical and biophysical research communications},
  volume    = {465},
  journal   = {Biochemical and biophysical research communications},
  number    = {3},
  publisher = {Elsevier},
  address   = {San Diego},
  issn      = {0006-291X},
  doi       = {10.1016/j.bbrc.2015.08.002},
  pages     = {356 -- 362},
  year      = {2015},
  abstract  = {Pulmonary arterial hypertension (PAH) is a fatal disease that eventually results in right heart failure and death. Current pharmacologic therapies for PAH are limited, and there are no drugs that could completely cure PAH. Enhanced activity of endothelin system has been implicated in PAH severity and endothelin receptor antagonists have been used clinically to treat PAH. However, there is limited experimental evidence on the direct role of enhanced endothelin system activity in PAL-I. Here, we investigated the correlation between endothelin-1 (ET-1) and PAH using ET-1 transgenic (ETTG) mice. Exposure to chronic hypoxia increased right ventricular pressure and pulmonary arterial wall thickness in ETTG mice compared to those in wild type mice. Of note, ETTG mice exhibited modest but significant increase in right ventricular pressure and vessel wall thickness relative to wild type mice even under normoxic conditions. To induce severe PAH, we administered SU5416, a vascular endothelial growth factor receptor inhibitor, combined with exposure to chronic hypoxia. Treatment with SU5416 modestly aggravated hypoxia-induced pulmonary hypertension, right ventricular hypertrophy, and pulmonary arterial vessel wall thickening in ETTG mice in association with increased interleukin-6 expression in blood vessels. However, there was no sign of obliterative endothelial cell proliferation and plexiform lesion formation in the lungs. These results demonstrated that enhanced endothelin system activity could be a causative factor in the development of PAH and provided rationale for the inhibition of endothelin system to treat PAH. (C) 2015 Elsevier Inc. All rights reserved.},
  language  = {en}
}
@article{StaschSchlossmannHocher2015,
  author    = {Stasch, Johannes-Peter and Schlossmann, Jens and Hocher, Berthold},
  title     = {Renal effects of soluble guanylate cyclase stimulators and activators: A review of the preclinical evidence},
  series = {Current opinion in pharmacology},
  volume    = {21},
  journal   = {Current opinion in pharmacology},
  publisher = {Elsevier},
  address   = {Oxford},
  issn      = {1471-4892},
  doi       = {10.1016/j.coph.2014.12.014},
  pages     = {95 -- 104},
  year      = {2015},
  abstract  = {Direct stimulation of soluble guanylate cyclase (sGC) is emerging as a potential new approach for the treatment of renal disorders. sGC catalyzes the formation of cyclic guanosine monophosphate (cGMP), deficiency of which is implicated in the pathogenesis of chronic kidney disease (CKD). Therefore, new classes of drugs sGC stimulators and activators are being investigated in preclinical models under conditions where nitric oxide is deficient. In preclinical models with different etiologies of CKD, the sGC stimulators BAY 41-2272, BAY 41-8543, BAY 60-4552, riociguat and vericiguat and the sGC activators cinaciguat, ataciguat, BI 703704 and GSK2181236A have shown consistently renoprotective effects. Clinical trials are required to confirm these findings in humans, and to ascertain whether these agents could provide a future alternative to guideline-recommended treatments.},
  language  = {en}
}