A5025085896- Blood Coagulation and Thrombosis Mechanisms
- Renal Diseases and Glomerulopathies
- Chronic Kidney Disease and Diabetes
- Pregnancy and preeclampsia studies
- Renin-Angiotensin System Studies
- Apelin-related biomedical research
- Endoplasmic Reticulum Stress and Disease
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Inflammasome and immune disorders
- Lipoproteins and Cardiovascular Health
- Phagocytosis and Immune Regulation
- Mesenchymal stem cell research
- Hematopoietic Stem Cell Transplantation
- Complement system in diseases
- Pancreatic function and diabetes
- Autophagy in Disease and Therapy
- Renal and related cancers
- Acute Kidney Injury Research
- Neurological Disorders and Treatments
- Signaling Pathways in Disease
- Antiplatelet Therapy and Cardiovascular Diseases
- Cardiovascular Function and Risk Factors
- Advanced Glycation End Products research
- Cancer Cells and Metastasis
- Epigenetics and DNA Methylation
University Medical Center of the Johannes Gutenberg University Mainz
2017-2024
Johannes Gutenberg University Mainz
2017-2024
University Medical Center
2021
Otto-von-Guericke University Magdeburg
2011-2020
University Hospital Magdeburg
2011-2014
Klinikum Magdeburg
2013-2014
Heidelberg University
2005-2011
University Hospital Heidelberg
2008-2009
Tongji Hospital
2009
Huazhong University of Science and Technology
2009
Diabetic nephropathy is a growing health concern with characteristic sterile inflammation. As the underlying mechanisms of this inflammation remain poorly defined, specific therapies targeting in diabetic are lacking. Intriguingly, an association inflammasome activation has recently been shown, but pathophysiological relevance finding remains unknown. Within glomeruli, was detected endothelial cells and podocytes humans mice glucose-stressed glomerular vitro. Abolishing Nlrp3 or caspase-1...
Abstract Endoplasmic reticulum (ER) stress is associated with diabetic nephropathy (DN), but its pathophysiological relevance and the mechanisms that compromise adaptive ER signalling in podocytes remain unknown. Here we show nuclear translocation of transcription factor spliced X-box binding protein-1 (sXBP1) selectively impaired DN, inducing activating factor-6 (ATF6) C/EBP homology protein (CHOP). Podocyte-specific genetic ablation XBP1 or inducible expression ATF6 mice aggravates DN....
The coagulation protease activated protein C (aPC) confers cytoprotective effects in various vitro and vivo disease models, including diabetic nephropathy. nephroprotective effect may be related to antioxidant of aPC. However, the mechanism through which aPC convey these functional relevance properties remain unknown. Here, we show that endogenous exogenous prevents glomerular accumulation oxidative stress markers redox-regulating p66 Shc experimental These were predominately observed...
Glomerular apoptosis may contribute to diabetic nephropathy (dNP), but the pathophysiologic relevance of this process remains obscure. Here, we administered two partially disjunct polycaspase inhibitors in 8-week-old (db/db) mice: M-920 (inhibiting caspase-1, -3, -4, -5, -6, -7, and -8) CIX caspase-3, -8, -10). Notably, despite reduction glomerular cell death caspase-3 activity by both inhibitors, only ameliorated dNP. Nephroprotection was associated with reduced renal caspase-1 inflammasome...
A lipid-protein autoimmunity target Several autoimmune diseases, including systemic lupus erythematosus and primary antiphospholipid syndrome, are characterized by the presence of antibodies (aPLs). These molecules can activate complement coagulation cascades, which contributes to pathologies such as thrombosis, stroke, pregnancy complications. Müller-Calleja et al. found that endothelial protein C receptor (EPCR) in complex with lysobisphosphatidic acid (LBPA) is cell-surface for aPL...
Ischemia-reperfusion injury (IRI) is the leading cause of ARF. A pathophysiologic role coagulation system in renal IRI has been established, but functional relevance thrombomodulin (TM)-dependent activated protein C (aPC) generation and intracellular targets aPC remain undefined. Here, we investigated TM-dependent therapeutic application a murine model an vitro hypoxia reoxygenation (HR) using proximal tubular cells. In IRI, endogenous levels were reduced. Genetic or reconstitution...
The integrity of genome is a prerequisite for healthy life. Indeed, defects in DNA repair have been associated with several human diseases, including tissue-fibrosis, neurodegeneration and cancer. Despite decades extensive research, the spatio-mechanical processes double-strand break (DSB)-repair, especially auxiliary factor(s) that can stimulate accurate timely repair, remained elusive. Here, we report an ATM-kinase dependent, unforeseen function nuclear isoform Receptor Advanced Glycation...
Established therapies for diabetic nephropathy (dNP) delay but do not prevent its progression. The shortage of established may reflect the inability to target tubular compartment. chemical chaperone tauroursodeoxycholic acid (TUDCA) ameliorates maladaptive endoplasmic reticulum (ER) stress signaling and experimental dNP. Additionally, TUDCA activates farnesoid X receptor (FXR), which is highly expressed in cells. We hypothesized that ER via FXR agonism specifically Indeed, induced expression...
Clinical studies failed to provide clear evidence for a proatherogenic role of hypercoagulability. This is in contrast the well-established detrimental hypercoagulability and thrombin during acute atherosclerotic complications. These seemingly opposing data suggest that might exert both antiatherogenic effects. We therefore investigated whether mediates beneficial effect de novo atherogenesis.De atherogenesis was evaluated 2 mouse models with hyperlipidemia genetically imposed...
Summary Coagulation and complement regulators belong to two interactive systems constituting emerging mechanisms of diabetic nephropathy. Thrombomodulin (TM) regulates both coagulation activation, in part through discrete domains. TM’s lectin like domain dampens while its EGF-like domains independently enhance activation the anticoagulant cytoprotective serine protease protein C (PC). A protective effect activated PC nephropathy is established. We hypothesised that TM controls independent...
Whereas it is generally perceived to be harmful, enhanced coagulation activation can also convey salutary effects. The high prevalence of the prothrombotic factor V Leiden (FVL) mutation in whites has been attributed a positive selection pressure (eg, resulting from reduced blood loss or improved survival sepsis). consequences activation, as observed FVL carriers, on microvascular diabetic complications remain unknown. We therefore investigated role nephropathy. In heterozygous homozygous...
Diabetic cardiomyopathy (DCM) is a major complication of diabetes, but its underlying mechanisms still remain unclear. The multifunctional protein Y-box binding protein-1 (YB-1) plays an important role in cardiac pathogenesis by regulating apoptosis, fibrosis, and pathological remodeling, whereas chronic DCM requires further investigation. Here, we report that the phosphorylation YB-1 at serine102 (S102) was markedly elevated streptozotocin-induced diabetic mouse hearts high glucose-treated...
Objective: Aortic dissection (AD), a life-threatening cardiovascular emergency, continues to impose high mortality due insufficient therapeutic options, as monotherapy targeting angiotensin II type 1 receptor (AT1R) demonstrates limited clinical efficacy. Approach and Results: Utilizing single-cell RNA sequencing, we identified integrin β3 critical driver of AD progression, with expression levels positively correlated disease severity. Histopathological validation in human specimens murine...
Background: Chronic diabetes accelerates vascular dysfunction often resulting in cardiomyopathy but underlying mechanisms remain unclear. Recent studies have shown that the deregulated unfolded protein response (UPR) dependent on highly conserved IRE1α-spliced X-box- binding (XBP1s) and endoplasmic reticulum stress (ER-Stress) plays a crucial role occurrence development of diabetic (DCM). In present study, we determined whether targeting MAPK/ERK pathway using MEK inhibitor U0126 could...
Abstract Obesity promotes endothelial dysfunction. Endothelial cells not only respond, but possibly actively promote the development of obesity and metabolic Our aim was to characterize role leptin receptors (LepR) for whole body metabolism diet-induced obesity. Mice with tamoxifen-inducible, Tie2.Cre-ER T2 -mediated deletion LepR in (End.LepR knockout, KO) were fed high-fat diet (HFD) 16 weeks. Body weight gain, serum levels, visceral adiposity adipose tissue inflammation more pronounced...
Absence of the leucine zipper transcription factor p45NF-E2 results in thrombocytopenia, impaired placental vascularization and intrauterine growth restriction (IUGR) mice. The mechanism underlying p45NF-E2-dependent defect IUGR remains unknown. Here, we show that (Nfe2) null mouse embryos is unrelated to establishing embryonic platelets platelet-released mediators are dispensable for placentation. Rather, p45NF-E2, which was hitherto thought be specific hematopoietic cells, expressed...
Significance Statement Signaling to integrins is complex and depends on ligands their binding sites. Signaling-competent integrin that protect podocyte function remain unknown. This study demonstrates the coagulation protease-activated protein C (aPC) binds via its RGD sequence integrin- β 3 . Disruption of aPC–integrin- interaction results in excess RhoA activation dysfunction. These findings identify RGD-mediated as a rheostat signaling, which disrupted diabetic nephropathy....