Research Area B

Endocrine functions and plasticity of PDGFR-β+ interstitial cells in the healthy and fibrotic kidney

Dr. Katharina Broeker
Physiology
Universität Regensburg

Dr. Anna Lena Forst
Physiology
Universität Regensburg

In this project, we aim to understand (patho-) physiological regulators of EPO production relevant for the recruitment of EPO-expressing cells as well as for their restricted expression pattern in healthy and diseased kidneys. Differences between subpopulations of interstitial cells with regard to the expression of distinct components of the hypoxia signaling pathway or their sensitivity to PHD inhibitor treatment as well as paracrine factors from neighboring cells will be analyzed as potential factors. In addition, freshly isolated fibroblasts and co-cultured renal cells will be used to examine the influence of the hypoxia signaling pathway, along with the purinergic and the TGF-β1 signaling pathway on EPO expression in vitro.

Urinary vesicles as signal carriers and markers of kidney function development

Prof. Dr. Hayo Castrop
Physiology
Universität Regensburg

Prof. Dr. Iris Heid
Genetische Epidemiologie
Universität Regensburg

B2 will address three specific aims. We will (i) establish new prognostic biomarkers in urinary vesicles to detect and predict early changes in renal function (vesicular albumin and vesicular podocalyxin), (ii) identify additional tagging proteins in urinary vesicles to gain insights into the types and state of the originating cells, and (iii) clarify the role of extracellular vesicles for intra-renal communication pathways. We will use a broad array of in vivo and in vitro methods and will exploit data from large population-based study groups, taking advantage of the joint expertise on the two PIs in renal (patho-) physiology and epidemiology/statistics, respectively.

Phenotypic and functional characterization of pro-fibrotic and pro-regenerative T cells in models of renal fibrosis

Prof. Dr. Matthias Mack
Nephrology
Universität Regensburg

Fibrosis caused by repetitive injuries is considered a major cause of organ failure. We developed an experimental system to study repetitive renal insults and found strong evidence for the generation of a “fibrotic memory”. CD4+ memory T cells and IL-3 were identified as key players in this process. In the next funding period, we would like to better understand how these T cells are activated and what downstream pathways lead to matrix production. In addition, we will investigate whether there are also counterbalancing anti-fibrotic T cells and study the impact of sodium chloride on fibrosis development.

Anti-inflammatory and tissue-protective effects of 2-oxoglutarate-dependent dioxygenase inhibition in progressive kidney disease

Prof. Dr. Carsten Willam
Medizinische Klinik 4 - Nephrologie und Hypertensiologie
Universitätsklinikum Erlangen

PD Dr. Gunnar Schley
Medizinische Klinik 4 - Nephrologie und Hypertensiologie
Universitätsklinikum Erlangen

Prof. Dr. Jonathan Jantsch
Institut für Medizinische Mikrobiologie, Immunologie und Hygiene
Universität Köln

In the last funding period, we found that 2-oxoglutarate dioxygenase inhibitors (2OGDi) reduce inflammation in the mouse adenine nephropathy model. According to our results, we hypothesize that 2OGDi-mediated inflammasome-inhibition reduces chronic renal inflammation, which requires immunoregulatory and renoprotective effects of immunoregulatory Nr4a1-positive mononuclear phagocytes (MNPs). In this funding period, we will investigate the role of intracellular Ca2+ balance and adenylate cyclases on 2OGDi-mediated inflammasome inhibition and we will explore the role of Nr4a1-positive MNPs in 2OGDi-dependent renoprotection.

Role of renal dendritic cell subpopulations in the inflammatory environment of acute kidney injury and kidney transplantation

Prof. Dr. Diana Dudziak
Hautklinik - Labor Biologie Dendritischer Zellen
Universitätsklinikum Erlangen

PD Dr. André Hörning
Kinder- und Jugendklinik
Universitätsklinikum Erlangen

This project aims to investigate the role and interplay of dendritic cell (DC) and tubular epithelial cell subpopulations during ischemia-reperfusion and renal transplantation in mice. DCs are among the first immune cells to respond to danger signals in the transplant environment. Understanding the signals of stressed tubular epithelial cells to the different DC subpopulations of donor and recipient will help identify the network of signals for the development of more specific and less toxic immunosuppressants in the future.