Ass-Prof. Dr.med.vet. Franziska Dengler

Die AG Dengler beschäftigt sich mit Epithelphysiologie, insbesondere im Bereich des Gastrointestinaltrakts. Dieses Epithel hat zwei wichtige, teils widersprüchliche Aufgaben: Zum einen müssen Nährstoffe, Elektrolyte und Wasser aus dem Lumen aufgenommen werden, um die Versorgung des Organismus mit diesen Substraten sicherzustellen. Andererseits bildet das Darmepithel eine Barriere gegen Antigene im Darmlumen. Zusätzlich zu dieser funktionellen Herausforderung sind die Enterozyten mit einer einzigartigen Perfusionssituation konfrontiert. Der apikale Zellpol grenzt an das anaerobe Lumen und die Perfusion von der basolateralen Seite her unterliegt abhängig vom Verdauungsstatus und anderen systemischen Anforderungen großen Schwankungen. Somit besteht ein enormer Sauerstoffgradient vom basalen zum apikalen Zellpol und die Zellen unterliegen regelmäßig einer sogenannten „physiologischen Hypoxie“. Hypoxie, d.h. eine Situation, in der der zelluläre Sauerstoffbedarf dessen Verfügbarkeit übersteigt, ist ein zentraler Faktor bei vielen pathologischen Situationen wie Schlaganfällen oder Myokardinfarkten und hat zumeist schwerwiegende Folgen. Im Gegensatz dazu verfügt das Darmepithel scheinbar über Strategien, um mit dieser Herausforderung umzugehen und stellt daher ein ideales Ziel dar, um erfolgreiche Mechanismen zur Anpassung an Hypoxie zu untersuchen.
Auch im gastrointestinalen Epithel ist diese Anpassung nicht immer erfolgreich. Mesenteriale Infarkte beim Menschen haben eine extrem ungünstige Prognose und enden größtenteils tödlich. In der Veterinärmedizin ist dieses Problem im Zusammenhang mit der Kolik des Pferdes nur allzu bekannt. Auch hier führen Obstruktionen, Strangulationen oder Thrombembolien zu lokaler Hypoxie mit schweren Komplikationen, die trotz Resektion des betroffenen Darmabschnitts regelmäßig zum Tod führen. Ein besseres Verständnis der Anpassungsmechanismen, die bei diesen Patienten stattfinden oder versagen, könnte daher zur Verbesserung der Therapiestrategien bei Mensch und Tier beitragen und steht daher im Mittelpunkt unserer Forschung. Neben Perfusionsproblemen ist Hypoxie auch mit entzündlichen Zuständen verbunden, beispielsweise im Rahmen von chronisch entzündlichen Darmerkrankungen (inflammatory bowel disease, IBD) oder Infektionserkrankungen. Daher werden auch Projekte bearbeitet, die die Rolle der hypoxischen Anpassung bei IBD sowie bei Infektionskrankheiten wie Kryptosporidiose untersuchen.

Ongoing projects

  • Adaptation mechanisms to hypoxia in the intestinal epithelium
  • Pathophysiology of the intestinal glucose transport in neonatal cryptosporidiosis in calves in vitro & in vivo
  • Influence of training age on animal welfare and performance parameters in Standardbred horses
  • Adaptation mechanisms in the intestinal epithelium in canine idiopathic inflammatory bowel disease

Pulications (short link) 1

 

Adaptation mechanisms to hypoxia in the intestinal epithelium

Abstract:

Mesenteric ischemia represents a dramatic pathology with a high mortality in humans. In a veterinary context, it is mirrored by strangulation colics of horses. The resulting hypoxia leads to severe complications and death of the patient. The intestinal epithelium normally exists in a state of “physiological hypoxia” and seems to have specific adaptation mechanisms to hypoxia that ensure its survival under physiological conditions. Understanding these mechanisms might represent a first step in the identification of therapeutic approaches, not only for patients undergoing mesenteric ischemia but maybe also for those suffering from other hypoxia-associated diseases of the gastrointestinal epithelium.

While a long-term-adaptation via the transcription factor hypoxia inducible factor (HIF) has been thoroughly investigated, it is still not clear how the short-term adaptation is mediated to ensure epithelial survival after a sudden onset of hypoxia.

We have shown a rapid functional adaptation of glucose transport across isolated jejunum epithelium under hypoxia. We have also found an activation of adenosine 5’-monophosphate-activated protein kinase (AMPK) in isolated epithelia and cultivated intestinal epithelial cells under hypoxia. AMPK might thus be the factor that induces a fast functional adaptation to hypoxia.

In future experiments, we will elucidate the involvement of AMPK in epithelial adaptation to hypoxia and its coordination with HIF activation. We propose that the uptake of nutrients into the enterocytes is enhanced under hypoxia to secure the cellular energy supply. Simultaneously, energy-dependent transport mechanisms are supplemented by energy-independent mechanisms and the epithelial barrier is reinforced. A coordination of AMPK and HIF signalling under hypoxia could be mediated by the HIF-prolyl-4-hydroxylase enzymes or by factor inhibiting HIF1a.

Funding: n.n.

 

Cooperation partners:

Univ.-Prof. Dr. med. vet. Florien Jenner, Vetmeduni Vienna

Univ.-Prof. Dr. med. vet. Maik Dahlhoff, Vetmeduni Vienna

Prof. Dr. med. vet. Janina Burk, Justus-Liebig-University Gießen

PD Dr. Doreen Scharner, University of Leipzig

Dr. med. vet. Nicole Verhaar, University of Veterinary Medicine Hanover, Foundation

 

Pathophysiology of the intestinal glucose transport in neonatal cryptosporidiosis in calves in vitro & in vivo

 

Abstract:

The infection of calves with Crypotosporidium parvum is a widespread disease that causes considerable losses, especially in neonatal animals, but also represents a zoonotic risk for humans. To date, there is no effective therapy. In addition, little is known about the interaction between the host cell and the intracellular stages of C. parvum, which makes the development of new therapeutic approaches difficult.

In previous studies, we were able to detect drastic changes in the expression of the glucose transporter (GLUT) 2 in infected enterocytes in a cell culture model. Since both the host cell and C. parvum are dependent on an optimal energy supply to promote their physiological barrier function or the maturation of the multiplication stages (meronts), influencing the epithelial glucose transport is a logical consequence. However, it is unclear to which of the above goals this regulation is (more) useful and how it is initiated, so that possible therapeutic implications require further investigation.

To check the transferability of these in vitro findings to the in vivo situation, we infected newborn calves with C. parvum or assigned them to a control group (uninfected). In addition to studies on gene and protein levels and localization of the glucose transport proteins, analogous to the findings already obtained in vitro, the glucose metabolism in the splanchnic area will be examined using non-radioactive tracer techniques to characterize the systemic glucose supply and utilization of the calf to clarify who (calf or parasite) will benefit from the modulated glucose transport.

 

Funding:

Starting grants of the School of Veterinary Medicine Leipzig

 

Cooperation partners:

Dr. med. vet. Cora Delling, University of Leipzig

Prof. Dr. med. vet. Reiner Ulrich, University of Leipzig

PD Dr. med. vet. Harald Hammon, Leibniz Institute for Farm Animal Biology Dummerstorf

Dr. med. vet. Lisa Bachmann, Leibniz Institute for Farm Animal Biology Dummerstorf

Dr. rer. nat. Wendy Liermann, Leibniz Institute for Farm Animal Biology Dummerstorf

 

Influence of training age on animal welfare and performance parameters in Standardbred horses

 

Abstract:

Animal welfare has gained increasing importance in the last years. Thus, also horses as high-performance athletes are looked upon in a different light from before. Whereas in earlier days horses were considered as means of transportation, warfare or rather sport instruments, nowadays they are companion animals. This also implies an increasing interest in optimizing the animals’ living and training conditions. In racing horses, the early onset of training and racing at 2 years of age is discussed very emotionally, although there are few studies available that could provide an impartial base for this discussion.

We will compare the performance and health status of horses participating in their first important race at 3 years of age with horses starting at 4 years of age. We hypothesize, that a protracted and more gentle training onset will lead to less injury and increased wellbeing at similar performance in the older horses compared to those beginning their career one year earlier.

 

Funding: n.n.

 

Cooperation partners:

Univ.-Prof. Dr. med. vet. Florien Jenner, Vetmeduni Vienna

Ao.Univ.-Prof. Dr. med. vet. Rupert Palme, Vetmeduni Vienna

Dr. rer. nat. Stefanie Lürzel, Vetmeduni Vienna

Dr. med. vet. Corinna Arnold, University of Leipzig

 

Adaptation mechanisms in the intestinal epithelium in canine idiopathic inflammatory bowel disease

 

Abstract:

Idiopathic inflammatory bowel disease (IBD) is an increasing problem in companion animals. Similar to human IBD, the pathophysiology has not been unraveled. A better understanding of intrinsic adaptation mechanisms might open up new therapeutic approaches. This is why we investigate these mechanisms as well as functional changes in transepithelial transport.

 

Funding:

Dres. Bruns-Foundation (scholarship to S. Kather, postgraduate student)

Starting grants of the School of Veterinary Medicine Leipzig

 

Cooperation partners:

Prof. Dr. med. vet. Romy M. Heilmann, University of Leipzig

  

Contact

University of Veterinary Medicine Vienna (Vetmeduni Vienna)
Veterinärplatz 1
A-1210 Vienna, Austria

Unit for Physiology, Pathophysiology and
Experimental Endocrinology
Building HA, Ground Floor

Office & Administrative Support,

Irene Nefischer:

+43-1-25077-4551
Irene.Nefischer(at)vetmeduni.ac.at

Monday - Thursday, 9-13h