The infiltration of inflammatory cells into hypoxic tissue microenvironments and subsequent formation of new blood vessels (angiogenesis) or remodeling of the existing vasculature are central features of physiological wound healing responses as well as the pathophysiological processes of tumor angiogenesis and tissue fibrosis both of which involve aspects of wound healing:
Inflammation-driven vascular remodeling connecting cancer progression, wound healing and fibrosis.
Organ fibrosis as well as tumor progression show pathological features that are reminiscent of a classical wound healing response. Tissue fibrosis that is characterized by excessive scarring and extracellular matrix deposition after tissue injury is nowadays considered as an aberrant and excessive wound healing response. Likewise, the tumor microenvironment is often referred to as the "never healing wound" an certain tumor types exhibit excessive extracellular matrix deposition and massive. In addition, chronic, unresolved organ fibrosis predisposes for malignant transformation and the development of cancer. Therefore, our work is based on the hypothesis that wound healing, organ fibrosis and tumor progression share strong mechanistic links. The prominent features of these processes are infiltration of immune cells and subsequent remodeling of the vasculature in response to hypoxia (low oxygen).
Exposure of cells to low oxygen tensions leads to activation of Hypoxia-inducible factors (HIFs), a family of basic-helix-loop-helix transcription factors, which are key mediators of cellular adaptation to an hypoxic environment. HIFs regulate the transcription of hundreds of genes that encode proteins involved in literally every aspect of cellular or whole body homeostasis, including energy metabolism and cell survival as well as erythropoiesis and angiogenesis.
Immune cells are able to release large amounts of angiogenic factors. By using in vivo models with conditional knockouts in different immune cell subsets, we investigate the effect of inflammatory angiogenesis in various physiological and pathophysiological processes. Current projects focus on the role of HIFs in distinct immune cell subsets and their impact on tissue fibrosis after injury as well as on the progression of malignant tumors.