Reviews of Physiology Biochemistry and Pharmacology最新文献

The body homeostasis is maintained mainly by the function of the kidneys, which regulate salt and water balance and excretion of metabolism waste products and xenobiotics. This important renal function is determined by the action of many transport systems, which are specifically expressed in the different parts of the nephron, the functional unit of the kidneys. These transport systems are involved, for example, in the reabsorption of sodium, glucose, and other important solutes and peptides from the primary urine. They are also important in the reabsorption of water and thereby production of a concentrated urine. However, several studies have shown the importance of transport systems for different tumor entities. Transport systems, for example, contributed to the proliferation and migration of cancer cells and thereby on tumor progression. They could also serve as drug transporters that could enable drug resistance by outward transport of, for example, chemotherapeutic agents and other drugs. Although many renal transporters have been characterized in detail with respect to the significance for proper kidney function, their role in renal cancer progression is less known. Here, we describe the types of renal cancer and review the studies that analyzed the role of organic cation transporters of the SLC22-family and of the aquaporin water channel family in kidney tumors.

The development and function of a particular organ and the pathogenesis of various diseases remain intimately linked to the features of each cell type in the organ. Conventional messenger RNA- or protein-based methodologies often fail to elucidate the contribution of rare cell types, including some subpopulations of stem cells, short-lived progenitors and circulating tumour cells, thus hampering their applications in studies regarding organ development and diseases. The scRNA-seq technique represents a new approach for determining gene expression variability at the single-cell level. Organoids are new preclinical models that recapitulate complete or partial features of their original organ and are thought to be superior to cell models in mimicking the sophisticated spatiotemporal processes of the development and regeneration and diseases. In this review, we highlight recent advances in the field of scRNA-seq, organoids and their current applications and summarize the advantages of using a combination of scRNA-seq and organoid technology to model diseases and organ development.

Cyclic AMP and Ca²⁺ are the first second or intracellular messengers identified, unveiling the cellular mechanisms activated by a plethora of extracellular signals, including hormones. Cyclic AMP generation is catalyzed by adenylyl cyclases (ACs), which convert ATP into cAMP and pyrophosphate. By the way, Ca²⁺, as energy, can neither be created nor be destroyed; Ca²⁺ can only be transported, from one compartment to another, or chelated by a variety of Ca²⁺-binding molecules. The fine regulation of cytosolic concentrations of cAMP and free Ca²⁺ is crucial in cell function and there is an intimate cross-talk between both messengers to fine-tune the cellular responses. Cancer is a multifactorial disease resulting from a combination of genetic and environmental factors. Frequent cases of cAMP and/or Ca²⁺ homeostasis remodeling have been described in cancer cells. In those tumoral cells, cAMP and Ca²⁺ signaling plays a crucial role in the development of hallmarks of cancer, including enhanced proliferation and migration, invasion, apoptosis resistance, or angiogenesis. This review summarizes the cross-talk between the ACs/cAMP and Ca²⁺ intracellular pathways with special attention to the functional and reciprocal regulation between Orai1 and AC8 in normal and cancer cells.

Our mathematical model of epithelial transport (Larsen et al. Acta Physiol. 195:171-186, 2009) is extended by equations for currents and conductance of apical SGLT2. With independent variables of the physiological parameter space, the model reproduces intracellular solute concentrations, ion and water fluxes, and electrophysiology of proximal convoluted tubule. The following were shown: 1. Water flux is given by active Na⁺ flux into lateral spaces, while osmolarity of absorbed fluid depends on osmotic permeability of apical membranes. 2. Following aquaporin "knock-out," water uptake is not reduced but redirected to the paracellular pathway. 3. Reported decrease in epithelial water uptake in aquaporin-1 knock-out mouse is caused by downregulation of active Na⁺ absorption. 4. Luminal glucose stimulates Na⁺ uptake by instantaneous depolarization-induced pump activity ("cross-talk") and delayed stimulation because of slow rise in intracellular [Na⁺]. 5. Rate of fluid absorption and flux of active K⁺ absorption would have to be attuned at epithelial cell level for the [K⁺] of the absorbate being in the physiological range of interstitial [K⁺]. 6. Following unilateral osmotic perturbation, time course of water fluxes between intraepithelial compartments provides physical explanation for the transepithelial osmotic permeability being orders of magnitude smaller than cell membranes' osmotic permeability. 7. Fluid absorption is always hyperosmotic to bath. 8. Deviation from isosmotic absorption is increased in presence of glucose contrasting experimental studies showing isosmotic transport being independent of glucose uptake. 9. For achieving isosmotic transport, the cost of Na⁺ recirculation is predicted to be but a few percent of the energy consumption of Na⁺/K⁺ pumps.

Chemokine receptors, a diverse group within the seven-transmembrane G protein-coupled receptor superfamily, are frequently overexpressed in malignant tumors. Ligand binding activates multiple downstream signal transduction cascades that drive tumor growth and metastasis, resulting in poor clinical outcome. These receptors are thus considered promising targets for anti-tumor therapy. This article reviews recent studies on the expression and function of CXC chemokine receptors in various tumor microenvironments and recent developments in cancer therapy using CXC chemokine receptor antagonists.

The juxtaglomerular renin-producing cells (RPC) of the kidney are referred to as the major source of circulating renin. Renin is the limiting factor in renin-angiotensin system (RAS), which represents a proteolytic cascade in blood plasma that plays a central role in the regulation of blood pressure. Further cells disseminated in the entire organism express renin at a low level as part of tissue RASs, which are thought to locally modulate the effects of systemic RAS. In recent years, it became increasingly clear that the renal RPC are involved in developmental, physiological, and pathophysiological processes outside RAS. Based on recent experimental evidence, a novel concept emerges postulating that next to their traditional role, the RPC have non-canonical RAS-independent progenitor and renoprotective functions. Moreover, the RPC are part of a widespread renin lineage population, which may act as a global stem cell pool coordinating homeostatic, stress, and regenerative responses throughout the organism. This review focuses on the RAS-unrelated functions of RPC - a dynamic research area that increasingly attracts attention.

Renal fibrosis is the final pathological process common to any ongoing, chronic kidney injury or maladaptive repair. Renal fibrosis is considered to be closely related to various cell types, such as fibroblasts, myofibroblasts, T cells, and other inflammatory cells. Multiple types of cells regulate renal fibrosis through the recruitment, proliferation, and activation of fibroblasts, and the production of the extracellular matrix. Cell trafficking is orchestrated by a family of small proteins called chemokines. Chemokines are cytokines with chemotactic properties, which are classified into 4 groups: CXCL, CCL, CX3CL, and XCL. Similarly, chemokine receptors are G protein-coupled seven-transmembrane receptors classified into 4 groups: XCR, CCR, CXCR, and CX3CR. Chemokine receptors are also implicated in the infiltration, differentiation, and survival of functional cells, triggering inflammation that leads to fibrosis development. In this review, we summarize the different chemokine receptors involved in the processes of fibrosis in different cell types. Further studies are required to identify the molecular mechanisms of chemokine signaling that contribute to renal fibrosis.

Elevated levels of plasma cholesterol, impaired vascular wall, and presence of inflammatory macrophages are important atherogenic risk factors contributing to atherosclerotic plaque formation and progression. The interventions modulating these risk factors have been found to protect against atherosclerosis development and to decrease atherosclerosis-related cardiovascular disorders. Nutritional approaches involving supplements followed by improving dietary habits and lifestyle have become growingly attractive and acceptable methods used to control atherosclerosis risk factors, mainly high levels of plasma cholesterol. There are a large number of studies that show berberine, a plant bioactive compound, could ameliorate atherosclerosis-related risk factors. In the present literature review, we put together this studies and provide integrated evidence that exhibits berberine has the potential atheroprotective effect through reducing increased levels of plasma cholesterol, particularly low-density lipoprotein (LDL) cholesterol (LDL-C) via LDL receptor (LDLR)-dependent and LDL receptor-independent mechanisms, inhibiting migration and inflammatory activity of macrophages, improving the functionality of endothelial cells via anti-oxidant activities, and suppressing proliferation of vascular smooth muscle cells. In conclusion, berberine can exert inhibitory effects on the atherosclerotic plaque development mainly through LDL-lowering activity and suppressing atherogenic functions of mentioned cells. As the second achievement of this review, among the signaling pathways through which berberine regulates intracellular processes, AMP-activated protein kinase (AMPK) has a central and critical role, showing that enhancing activity of AMPK pathway can be considered as a promising therapeutic approach for atherosclerosis treatment.

The chapter 'Stationary and Nonstationary Ion and Water Flux Interactions in Kidney Proximal Tubule: Mathematical Analysis of Isosmotic Transport by a Minimalistic Model' has now been made available open access under a CC BY 4.0 license.

Familial hypercholesterolemia (FH) is a frequent autosomal genetic disease characterized by elevated concentrations of low-density lipoprotein cholesterol (LDL) from birth with increased risk of premature atherosclerotic complications. Accumulating evidence has shown enhanced inflammation in patients with FH. In vessels, the deposition of modified cholesterol lipoproteins triggers local inflammation. Then, inflammation facilitates fatty streak formation by activating the endothelium to produce chemokines and adhesion molecules. This process eventually results in the uptake of vascular oxidized LDL (OxLDL) by scavenger receptors in monocyte-derived macrophages and formation of foam cells. Further leukocyte recruitment into the sub-endothelial space leads to plaque progression and activation of smooth muscle cells proliferation. Several inflammatory biomarkers have been reported in this setting which can be directly synthetized by activated inflammatory/vascular cells or can be indirectly produced by organs other than vessels, e.g., liver. Of note, inflammation is boosted in FH patients. Inflammatory biomarkers might improve the risk stratification for coronary heart disease and predict atherosclerotic events in FH patients. This review aims at summarizing the current knowledge about the role of inflammation in FH and the potential application of inflammatory biomarkers for cardiovascular risk estimation in these patients.