Tanja Herrler

Bio: Tanja Herrler is an academic researcher from Ludwig Maximilian University of Munich. The author has contributed to research in topics: Renal function & Ischemia. The author has an hindex of 10, co-authored 34 publications receiving 2916 citations. Previous affiliations of Tanja Herrler include Shanghai Jiao Tong University.

The intrinsic renal compartment syndrome: new perspectives in kidney transplantation.

Abstract: PURPOSE Inflammatory edema after ischemia-reperfusion may impair renal allograft function after kidney transplantation. This study examines the effect of edema-related pressure elevation on renal function and describes a simple method to relieve pressure within the renal compartment. METHODS Subcapsular pressure at 6, 12, 24, 48 hr, and 18 days after a 45 min warm ischemia was determined in a murine model of renal ischemia-reperfusion injury. Renal function was measured by Tc-MAG3 scintigraphy and laser Doppler perfusion. Structural damage was assessed by histologic analysis. As a therapeutic approach, parenchymal pressure was relieved by a standardized circular 0.3 mm incision at the lower pole of the kidney capsule. RESULTS Compared with baseline (0.9+/-0.3 mm Hg), prolonged ischemia was associated with a sevenfold increase in subcapsular pressure 6 hr after ischemia (7.0+/-1.0 mm Hg; P<0.001). Pressure levels remained significantly elevated for 24 hr. Without therapy, a significant decrease in functional parameters was found with considerably reduced tubular excretion rate (33+/-3.5%, P<0.001) and renal perfusion (64.5+/-6.8%, P<0.005). Histologically, severe tissue damage was found. Surgical pressure relief was able to significantly prevent loss of tubular excretion rate (62.5+/-6.8%, P<0.05) and renal blood flow (96.2+/-4.8%; P<0.05) and preserved the integrity of renal structures. CONCLUSIONS Our data support the hypothesis of the existence of a renal compartment syndrome as a consequence of ischemia-reperfusion injury. Surgical pressure relief effectively prevented functional and structural renal impairment, and we speculate that this approach might be of value for improving graft function after renal transplantation.

An updated review of mechanotransduction in skin disorders: transcriptional regulators, ion channels, and microRNAs

Abstract: The skin is constantly exposed and responds to a wide range of biomechanical cues. The mechanobiology of skin has already been known and applied by clinicians long before the fundamental molecular mechanisms of mechanotransduction are elucidated. Despite increasing knowledge on the mediators of biomechanical signaling such as mitogen-associated protein kinases, Rho GTPases or FAK-ERK pathways, the key elements of mechano-responses transcription factors, and mechano-sensors remain unclear. Recently, canonical biochemical components of Hippo and Wnt signaling pathway YAP and β-catenin were found to exhibit undefined mechanical sensitivity. Mechanical forces were identified to be the dominant regulators of YAP/TAZ activity in a multicellular context. Furthermore, different voltage or ligand sensitive ion channels in the cell membrane exhibited their mechanical sensitivity as mechano-sensors. Additionally, a large number of microRNAs have been confirmed to regulate cellular behavior and contribute to various skin disorders under mechanical stimuli. Mechanosensitive (MS) microRNAs could not only be activated by distinct mechanical force pattern, but also responsively target MS sensors such as e-cadherin and cytoskeleton constituent RhoA. Thus, a comprehensive understanding of this regulatory network of cutaneous mechanotransduction will facilitate the development of novel approaches to wound healing, hypertrophic scar formation, skin regeneration, and the progression or initiation of skin diseases.

Prostaglandin E positively modulates endothelial progenitor cell homeostasis: an advanced treatment modality for autologous cell therapy.

Abstract: Aims: The mobilization of endothelial progenitor cells (EPC) and their functioning in postnatal neovascularization are tightly regulated. To identify new modulators of EPC homeostasis, we screened biologically active prostaglandin E compounds for their effects on EPC production, trafficking and function. Methods and Results: We found that EPC are a rich source for prostaglandin E2 (PGE2), stimulating their number and function in an auto- and paracrine manner. In vivo blockade of PGE2 production by selective cyclooxygenase-2 inhibition virtually abrogated ischemia-induced EPC mobilization demonstrating its crucial role in EPC homeostasis following tissue ischemia. Conversely, ex vivo treatment of isolated EPC with the clinically approved PGE1 analogue alprostadil enhanced EPC number and function. These effects were mediated by increased expression of the chemokine receptor CXCR4 and were dependent on nitric oxide synthase activity. Most importantly, ex vivo PGE1 pretreatment of isolated EPC significantly enhanced their neovascularization capacity in a murine model of hind limb ischemia as assessed by laser Doppler analysis, exercise stress test and immunohistochemistry. Conclusions: The conserved role for PGE in the regulation of EPC homeostasis suggests that ex vivo modulation of the prostaglandin pathway in isolated progenitor cells may represent a novel and safe strategy to facilitate cell-based therapies.

Fourier-transform method of fringe-pattern analysis for computer-based topography and interferometry

Abstract: A fast-Fourier-transform method of topography and interferometry is proposed. By computer processing of a noncontour type of fringe pattern, automatic discrimination is achieved between elevation and depression of the object or wave-front form, which has not been possible by the fringe-contour-generation techniques. The method has advantages over moire topography and conventional fringe-contour interferometry in both accuracy and sensitivity. Unlike fringe-scanning techniques, the method is easy to apply because it uses no moving components.

Cancer stem cells in solid tumours: accumulating evidence and unresolved questions

Abstract: Solid tumours are an enormous cancer burden and a major therapeutic challenge. The cancer stem cell (CSC) hypothesis provides an attractive cellular mechanism to account for the therapeutic refractoriness and dormant behaviour exhibited by many of these tumours. There is increasing evidence that diverse solid tumours are hierarchically organized and sustained by a distinct subpopulation of CSCs. Direct evidence for the CSC hypothesis has recently emerged from mouse models of epithelial tumorigenesis, although alternative models of heterogeneity also seem to apply. The clinical relevance of CSCs remains a fundamental issue but preliminary findings indicate that specific targeting may be possible.

EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer

Abstract: Tumors are cellularly and molecularly heterogeneous, with subsets of undifferentiated cancer cells exhibiting stem cell-like features (CSCs). Epithelial to mesenchymal transitions (EMT) are transdifferentiation programs that are required for tissue morphogenesis during embryonic development. The EMT process can be regulated by a diverse array of cytokines and growth factors, such as transforming growth factor (TGF)-β, whose activities are dysregulated during malignant tumor progression. Thus, EMT induction in cancer cells results in the acquisition of invasive and metastatic properties. Recent reports indicate that the emergence of CSCs occurs in part as a result of EMT, for example, through cues from tumor stromal components. Recent evidence now indicates that EMT of tumor cells not only causes increased metastasis, but also contributes to drug resistance. In this review, we will provide potential mechanistic explanations for the association between EMT induction and the emergence of CSCs. We will also highlight recent studies implicating the function of TGF-β-regulated noncoding RNAs in driving EMT and promoting CSC self-renewal. Finally we will discuss how EMT and CSCs may contribute to drug resistance, as well as therapeutic strategies to overcome this clinically.