Search results for "signal transduction."
showing 10 items of 1278 documents
The lipoprotein receptor LRP1 modulates sphingosine-1-phosphate signaling and is essential for vascular development
2014
Low density lipoprotein receptor-related protein 1 (LRP1) is indispensable for embryonic development. Comparing different genetically engineered mouse models, we found that expression of Lrp1 is essential in the embryo proper. Loss of LRP1 leads to lethal vascular defects with lack of proper investment with mural cells of both large and small vessels. We further demonstrate that LRP1 modulates Gi-dependent sphingosine-1-phosphate (S1P) signaling and integrates S1P and PDGF-BB signaling pathways, which are both crucial for mural cell recruitment, via its intracellular domain. Loss of LRP1 leads to a lack of S1P-dependent inhibition of RAC1 and loss of constraint of PDGF-BB-induced cell migra…
The transmembrane receptor Uncoordinated5 (Unc5) is essential for heart lumen formation in Drosophila melanogaster
2011
AbstractTransport of liquids or gases in biological tubes is fundamental for many physiological processes. Our knowledge on how tubular organs are formed during organogenesis and tissue remodeling has increased dramatically during the last decade. Studies on different animal systems have helped to unravel some of the molecular mechanisms underlying tubulogenesis. Tube architecture varies dramatically in different organs and different species, ranging from tubes formed by several cells constituting the cross section, tubes formed by single cells wrapping an internal luminal space or tubes that are formed within a cell. Some tubes display branching whereas others remain linear without interse…
Angiogenic activity of breast cancer patients' monocytes reverted by combined use of systems modeling and experimental approaches.
2015
Angiogenesis plays a key role in tumor growth and cancer progression. TIE-2-expressing monocytes (TEM) have been reported to critically account for tumor vascularization and growth in mouse tumor experimental models, but the molecular basis of their pro-angiogenic activity are largely unknown. Moreover, differences in the pro-angiogenic activity between blood circulating and tumor infiltrated TEM in human patients has not been established to date, hindering the identification of specific targets for therapeutic intervention. In this work, we investigated these differences and the phenotypic reversal of breast tumor pro-angiogenic TEM to a weak pro-angiogenic phenotype by combining Boolean m…
Coagulation signaling and cancer immunotherapy.
2019
The last decades have delineated many interactions of the hemostatic system with cancer cells that are pivotal for cancer-associated thrombosis, angiogenesis and metastasis. Expanding evidence shows that platelets, the tissue factor pathway, and proteolytic signaling involving protease-activated receptors (PARs) are also central players in innate and adaptive immunity. Recent studies in immune-competent mice have uncovered new immune-evasive roles of coagulation signaling networks in the development and growth of different preclinical tumor models. Tumor-type specific PAR1 signaling facilitates the escape from immune surveillance by cytotoxic T cells. In addition, tumor-associated macrophag…
The role of endosomal toll-like receptors in bacterial recognition
2012
BACKGROUND: Infections caused by extracellular Gram positive bacteria are still a major health problems. Better understanding of the mechanisms underlying immune responses to these organisms is key to develop pharmacological agents, including vaccines, to control these infections. OBJECTIVE AND PERSPECTIVES: The objective of this review is to highlight the importance of nucleic acid-sensing, intracellular Toll-like receptors in innate immune recognition and in host defenses against extracellular bacteria. CONCLUSIONS: Toll-like receptors 7 and 9 have a major role in inducing host-protective type I interferon responses in conventional dendritic cells in response to streptococci and other ext…
Resistance of p53 knockout cells to doxorubicin is related to reduced formation of DNA strand breaks rather than impaired apoptotic signaling
2003
The anthracycline doxorubicin (adriamycin) is an important chemotherapeutic agent used in the treatment of solid epithelial and mesenchymal tumors as well as leukemias. A variety of mechanisms has been proposed to be involved in doxorubicin-induced cytotoxicity such as DNA intercalation, oxidative stress, DNA strand breakage by inhibition of topoisomerase II, activation of death receptors, and altered p53 expression. Concerning doxorubicin resistance and p53 status data reported are contradictory. Here, we show that mouse fibroblasts deficient in p53 (p53(-/-)) are more resistant to doxorubicin than p53 wild-type (p53 wt) cells. This is in contrast to other genotoxic agents (UV-light, alkyl…
Inducers of heme oxygenase-1.
2008
Heme oxygenase-1 (HO-1) is an inducible rate-limiting enzyme which catalyzes group heme into carbon monoxide, iron and bilirubin. In the recent years, HO-1 expression has been reported as an important protective endogenous mechanism against physical, chemical and biological stress. In this regard, induction of this enzyme has shown beneficial effects in several pathologic conditions, such as inflammatory processes, atherosclerosis, carcinogenesis, ischemia-reperfusion systems or degenerative diseases. Complex intracellular signalling cascades mediate the expression of HO-1 in response to external stimuli, Transcription factors, as nuclear factor E2-related factor-2, activator protein-1, and…
Carbon Monoxide-Releasing Molecules: A Pharmacological Expedient to Counteract Inflammation
2008
Carbon monoxide (CO) mediates many of the biological effects that are attributed to heme oxygenase (HO), the enzyme responsible for CO production in mammals. Antioxidant and anti-inflammatory activities of HO-1, the inducible isoform of heme oxygenase, have been demonstrated in a variety of disease models and a therapeutic exploitation of this pathway is currently under scrutiny. In this context, the liberation of CO from CO-releasing molecules (CO-RMs) is extremely attractive as these compounds may form the basis of a new class of pharmaceuticals. Recent investigations indicate that HO-1 and CO modulate important processes in chronic inflammation; these include the control of immune respon…
Role of the Non-Canonical RNAi Pathway in the Antifungal Resistance and Virulence of Mucorales
2021
Mucorales are the causal agents for the lethal disease known as mucormycosis. Mortality rates of mucormycosis can reach up to 90%, due to the mucoralean antifungal drug resistance and the lack of effective therapies. A concerning urgency among the medical and scientific community claims to find targets for the development of new treatments. Here, we reviewed different studies describing the role and machinery of a novel non-canonical RNAi pathway (NCRIP) only conserved in Mucorales. Its non-canonical features are the independence of Dicer and Argonaute proteins. Conversely, NCRIP relies on RNA-dependent RNA Polymerases (RdRP) and an atypical ribonuclease III (RNase III). NCRIP regulates the…