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Research

Our group is interested in epithelial physiology, especially in the gastrointestinal tract
This epithelium has two important, partially contradicting tasks: On the one hand, nutrients, electrolytes and water must be absorbed from the lumen to ensure that the organism is supplied with these substrates. On the other hand, the intestinal epithelium forms a barrier against antigens in the intestinal lumen.

In addition to this functional challenge, the enterocytes are confronted with a unique perfusion situation. On one side of the cells is the anaerobic lumen and from the basolateral side the perfusion varies depending on the digestive status and other systemic requirements. Thus, there is an oxygen gradient from the basal to the apical cell pole and the cells subsist in a so called "physiological hypoxia".
 
Hypoxia, i.e., a situation in which the cellular oxygen demand exceeds its availability, is a central factor in many pathological situations such as strokes or myocardial infarction and usually has serious consequences. During “physiological hypoxia”, the intestinal epithelium appears to have strategies to deal with this challenge and is therefore an ideal target for studying successful adaptation mechanisms to hypoxia.

Confocal laser scanning microscopy of cultivated equine jejunum epithelium cells (cytokeratin green, nuclei blue).

 

 

This adaptation is not always successful in the gastrointestinal epithelium either. Mesenteric infarcts in humans have an extremely unfavorable prognosis and are mostly fatal. In veterinary medicine, this problem is all too well known in equine colic. Here, obstructions, strangulations or thromboembolism lead to local hypoxia in the intestine with severe complications that are often fatal.

A better understanding of risk factors and the adaptation mechanisms that take place or fail in these patients could help improve therapeutic strategies in humans and animals and is therefore the focus of our research.

In addition to perfusion problems, hypoxia is also associated with inflammatory conditions, for example in the context of inflammatory bowel disease (IBD) or infectious diseases. Therefore, other projects aim to investigate the role of hypoxic adaptation in IBD as well as in infectious diseases such as cryptosporidiosis in calves.

 
We use a multitude of methods, ranging from primary cell and organoid culture to molecular biology and the Ussing chamber technique.

Ongoing projects
 

  • Adaptation mechanisms to hypoxia in the equine intestinal epithelium
     
  • Pathophysiology of the intestinal glucose transport in neonatal cryptosporidiosis in calves in vitro & in vivo
    (funded by a Starting Grant of the School of Veterinary Medicine, Leipzig University)
     
  • Panacea butyrate? Evaluation of production, effects and therapeutic potential in the equine colon
    (funded by the BMBWF: Sparkling Science 2.0)
  • Microbiota-derived butyrate in equine large intestinal disease: savior or super-villain? (funded by a Networking Seed Grant of the University of Veterinary Medicine Vienna)
     
  • Influence of training age on animal welfare and performance parameters in Standardbred horses
    (funded by the Association for the promotion of research in equestrian sport, FFP e.V.)
     
  • Adaptation mechanisms in the intestinal epithelium in canine idiopathic inflammatory bowel disease

Team

Anna Baltl – Diploma student

Jessica Gschossmann – Diploma student

Nina Liebminger – Bachelor student

Katharina Rumpl – Diploma student

Svea Schmidt – PhD student

Lena Stumbauer – Bachelor student

Christina Windhaber, Mag. med. vet., DVM – PhD student

Mimi von Zitzewitz - Diploma student

Top 10 publications

Dengler F, Sternberg F, Grages M, Kästner S, Verhaar N (2022): Adaptive mechanisms in no flow versus low flow ischemia in equine jejunum epithelium: different paths to the same destination. Frontiers in Veterinary Science; DOI: 10.3389/fvets.2022.947482.

Dengler F, Sova S, Salo AM, Mäki JM, Koivunen P, Myllyharju J (2021): Expression and Roles of Individual HIF Prolyl 4‐Hydroxylase Isoenzymes in the Regulation of the Hypoxia Response Pathway along the Murine Gastrointestinal Epithelium. International Journal of Molecular Sciences 22(8), 4038; DOI: 10.3390/ijms22084038.
 
Dengler F, Kraetzig A, Gäbel G (2021): Butyrate protects porcine colon epithelium from Hypoxia-induced damage on a functional level. Nutrients 13(2), 305; DOI: 10.3390/nu13020305.

Laitakari A, Tapio J, Mäkelä KA, Herzig K, Dengler F, Gylling H, Walkinshaw G, Myllyharju J, Dimova EY, Serpi R, Koivunen P (2020): HIF-P4H-2 inhibition enhances intestinal fructose metabolism and induces thermogenesis protecting against NAFLD. Journal of Molecular Medicine. DOI: 10.1007/s00109-020-01903-0.
 
Delling C, Daugschies A, Bangoura B, Dengler F (2019) Cryptosporidium parvum alters glucose transport mechanisms in infected enterocytes. Parasitology Research 118 (12): 3429-41. doi: 10.1007/s00436-019-06471-y.
 
Dengler F, Gäbel G (2019): The fast lane of hypoxic adaptation: Glucose transport Is modulated via a HIF-hydroxylase-AMPK-axis in jejunum epithelium. International Journal of Molecular Sciences 20 (20). doi: 10.3390/ijms20204993.
 
Dengler F, Rackwitz R, Pfannkuche H, Gäbel G. (2018): Coping with hypoxia: adaptation of glucose transport mechanisms across equine jejunum epithelium. Journal of Equine Veterinary Science, 69: 1-10. DOI: 10.1016/j.jevs.2018.05.221.
 
Dengler F, Rackwitz R, Pfannkuche H, Gäbel G. (2017): Glucose transport across lagomorph jejunum epithelium is modulated by AMP-activated protein kinase (AMPK) under hypoxia. Journal of Applied Physiology (1985). DOI: 10.1152/japplphysiol.00436.2017.
 
Dengler F, Rackwitz R, Benesch F, Pfannkuche H, Gäbel G (2015): Both butyrate incubation and hypoxia upregulate genes involved in the ruminal transport of SCFA and their metabolites.  Journal of animal physiology and animal nutrition 99 (2), S. 379–390. DOI: 10.1111/jpn.12201.
 
Dengler F, Rackwitz R, Benesch F, Pfannkuche H, Gäbel G (2014): Bicarbonate-dependent transport of acetate and butyrate across the basolateral membrane of sheep rumen epithelium. Acta physiologica (Oxford, England) 210 (2), S. 403–414. DOI: 10.1111/apha.12155.