crosstalk
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Integrating important environmental signals with intrinsic developmental programmes is a crucial adaptive requirement for plant growth, survival, and reproduction. Key environmental cues include changes in several light variables, while important intrinsic (and highly interactive) regulators of many developmental processes include the phytohormones cytokinins (CKs) and ethylene. Here, we discuss the latest discoveries regarding the molecular mechanisms mediating CK/ethylene crosstalk at diverse levels of biosynthetic and metabolic pathways and their complex interactions with light. Furthermore, we summarize evidence indicating that multiple hormonal and light signals are integrated in the multistep phosphorelay (MSP) pathway, a backbone signalling pathway in plants. Inter alia, there are strong overlaps in subcellular localizations and functional similarities in components of these pathways, including receptors and various downstream agents. We highlight recent research demonstrating the importance of CK/ethylene/light crosstalk in selected aspects of plant development, particularly seed germination and early seedling development. The findings clearly demonstrate the crucial integration of plant responses to phytohormones and adaptive responses to environmental cues. Finally, we tentatively identify key future challenges to refine our understanding of the molecular mechanisms mediating crosstalk between light and hormonal signals, and their integration during plant life cycles.
- MeSH
- autoimunita MeSH
- beta-buňky MeSH
- buněčná smrt MeSH
- buňky NK imunologie MeSH
- diabetes mellitus 1. typu * etiologie imunologie prevence a kontrola MeSH
- lidé MeSH
- NKT buňky imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
- MeSH
- autoimunita MeSH
- beta-buňky MeSH
- buněčná smrt MeSH
- buňky NK imunologie MeSH
- diabetes mellitus 1. typu * etiologie imunologie prevence a kontrola MeSH
- lidé MeSH
- NKT buňky imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Dermal fibroblasts seem critical for epidermal maturation and differentiation and recent work demonstrated that diseased fibroblasts may drive pathophysiological processes. Nevertheless, still very little is known about the actual crosstalk between epidermal keratinocytes and dermal fibroblasts and the impact of dermal fibroblasts on epidermal maturation and differentiation. Aiming for a more fundamental understanding of the impact of the cellular crosstalk between keratinocytes and fibroblasts on the skin homeostasis, we generated full-thickness skin equivalents with and without fibroblasts and subsequently analysed them for the expression of skin differentiation markers, their barrier function, skin lipid content and epidermal cell signalling. Skin equivalents without fibroblasts consistently showed an impaired differentiation and dysregulated expression of skin barrier and tight junction proteins, increased skin permeability, and a decreased skin lipid/protein ratio. Most interestingly, impaired Ras/Raf/ERK/MEK signalling was evident in skin equivalents without fibroblasts. Our data clearly indicate that the epidermal-dermal crosstalk between keratinocytes and fibroblasts is critical for adequate skin differentiation and that fibroblasts orchestrate epidermal differentiation processes.
- MeSH
- buněčná diferenciace MeSH
- epidermální buňky metabolismus patologie MeSH
- epidermis metabolismus MeSH
- fibroblasty metabolismus MeSH
- homeostáza genetika fyziologie MeSH
- keratinocyty metabolismus patologie MeSH
- kožní absorpce MeSH
- kůže metabolismus patologie MeSH
- lidé MeSH
- permeabilita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The bone marrow microenvironment plays a decisive role in multiple myeloma progression and drug resistance. Chemokines are soluble mediators of cell migration, proliferation and survival and essentially modulate tumor progression and drug resistance. Here we investigated bone marrow-derived chemokines of naive and therapy-refractory myeloma patients and discovered that high levels of the chemokine CCL27, known so far for its role in skin inflammatory processes, correlated with worse overall survival of the patients. In addition, chemokine levels were significantly higher in samples from patients who became refractory to bortezomib at first line treatment compared to resistance at later treatment lines.In vitro as well as in an in vivo model we could show that CCL27 triggers bortezomib-resistance of myeloma cells. This effect was strictly dependent on the expression of the respective receptor, CCR10, on stroma cells and involved the modulation of IL-10 expression, activation of myeloma survival pathways, and modulation of proteasomal activity. Drug resistance could be totally reversed by blocking CCR10 by siRNA as well as blocking IL-10 and its receptor.From our data we suggest that blocking the CCR10/CCL27/IL-10 myeloma-stroma crosstalk is a novel therapeutic target that could be especially relevant in early refractory myeloma patients.
- MeSH
- apoptóza účinky léků MeSH
- bortezomib farmakologie MeSH
- chemokin CCL27 metabolismus MeSH
- chemorezistence * MeSH
- inhibitory proteasomu farmakologie MeSH
- interakce mezi receptory a ligandy účinky léků MeSH
- interleukin-10 genetika metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mnohočetný myelom farmakoterapie enzymologie genetika patologie MeSH
- nádorové buněčné linie MeSH
- nádorové mikroprostředí MeSH
- pohyb buněk účinky léků MeSH
- proliferace buněk účinky léků MeSH
- proteasomový endopeptidasový komplex metabolismus MeSH
- receptory CCR10 genetika metabolismus MeSH
- receptory interleukinu-10 genetika metabolismus MeSH
- RNA interference MeSH
- senioři MeSH
- signální transdukce účinky léků MeSH
- transfekce MeSH
- xenogenní modely - testy protinádorové aktivity MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
To maintain the activity of meristems is an absolute requirement for plant growth and development, and the role of the plant hormones auxin and cytokinin in apical meristem function is well established. Only little attention has been given, however, to the function of the reactive oxygen species (ROS) gradient along meristematic tissues and its interplay with hormonal regulatory networks. The interdependency between auxin-related, cytokinin-related and ROS-related circuits controls primary growth and development while modulating plant morphology in response to detrimental environmental factors. Because ROS interaction with redox-active compounds significantly affects the cellular redox gradient, the latter constitutes an interface for crosstalk between hormone and ROS signalling pathways. This review focuses on the mechanisms underlying ROS-dependent interactions with redox and hormonal components in shoot and root apical meristems which are crucial for meristems maintenance when plants are exposed to environmental hardships. We also emphasize the importance of cell type and the subcellular compartmentalization of ROS and redox networks to obtain a holistic understanding of how apical meristems adapt to stress.
The physiology of B cells is intimately connected with the function of their B-cell receptor (BCR). B-cell lymphomas frequently (dys)regulate BCR signalling and thus take advantage of this pre-existing pathway for B-cell proliferation and survival. This has recently been underscored by clinical trials demonstrating that small molecules (fosfamatinib, ibrutinib, idelalisib) inhibiting BCR-associated kinases (SYK, BTK, PI3K) have an encouraging clinical effect. Here we describe the current knowledge of the specific aspects of BCR signalling in diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, chronic lymphocytic leukaemia (CLL) and normal B cells. Multiple factors can contribute to BCR pathway (dys)regulation in these malignancies and the activation of 'chronic' or 'tonic' BCR signalling. In lymphoma B cells, the balance of initiation, amplitude and duration of BCR activation can be influenced by a specific immunoglobulin structure, the expression and mutations of adaptor molecules (like GAB1, BLNK, GRB2, CARD11), the activity of kinases (like LYN, SYK, PI3K) or phosphatases (like SHIP-1, SHP-1 and PTEN) and levels of microRNAs. We also discuss the crosstalk of BCR with other signalling pathways (NF-κB, adhesion through integrins, migration and chemokine signalling) to emphasise that the 'BCR inhibitors' target multiple pathways interconnected with BCR, which might explain some of their clinical activity.
- MeSH
- B-lymfocyty účinky léků metabolismus patologie MeSH
- chronická lymfatická leukemie farmakoterapie genetika metabolismus patologie MeSH
- difúzní velkobuněčný B-lymfom farmakoterapie genetika metabolismus patologie MeSH
- folikulární lymfom farmakoterapie genetika metabolismus patologie MeSH
- inhibitory proteinkinas terapeutické užití MeSH
- interakce mezi receptory a ligandy * MeSH
- lidé MeSH
- protinádorové látky terapeutické užití MeSH
- receptory antigenů B-buněk antagonisté a inhibitory genetika metabolismus MeSH
- regulace genové exprese u leukemie * MeSH
- signální transdukce genetika MeSH
- tyrosinkinasy antagonisté a inhibitory genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Obesity is a major health problem that is increasing in an alarming rate and is associated with an increased prevalence of cardiovascular morbidity and mortality. New strategies to combat obesity epidemic are urgently needed, but gaps in understanding of obesity pathogenesis continue to limit progress in this goal. This review aims at discussing the neural aspects of obesity and the brain potential role in energy balance, also to contribute in the complex solution of obesity puzzle on neurological basis. The hypothalamic region of the brain is the center that plays an important role in the control of feeding and its related behaviors. A better understanding of its role and how it is affected by neuroendocrine and adipokines signaling might be helpful in developing new pharmacological therapy for obesity. Also, this article highlights different mechanisms by which altered brain signaling and hypothalamic inflammation predispose to diet–induced obesity.
- MeSH
- adiponektin metabolismus MeSH
- chuť k jídlu fyziologie MeSH
- endoplazmatické retikulum metabolismus MeSH
- energetický metabolismus MeSH
- ghrelin metabolismus MeSH
- hypothalamus * imunologie patofyziologie MeSH
- leptin metabolismus MeSH
- lidé MeSH
- neuropeptidy MeSH
- NF-kappa B MeSH
- obezita * metabolismus patofyziologie MeSH
- protein SOCS3 MeSH
- renin-angiotensin systém MeSH
- signální transdukce MeSH
- systém hypofýza - nadledviny MeSH
- zánět MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
