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International Journal of Molecular... Oct 2020The renin-angiotensin system (RAS) is a peptidic system known mainly for its roles in the maintenance of blood pressure and electrolyte and fluid homeostasis. However,... (Review)
Review
The renin-angiotensin system (RAS) is a peptidic system known mainly for its roles in the maintenance of blood pressure and electrolyte and fluid homeostasis. However, several tissues and cells have been described to possess an intrinsic RAS that acts locally through different paracrine and autocrine mechanisms. In the male reproductive system, several components of this system have been observed in various organs and tissues, such as the testes, spermatozoa and seminal fluid. Some functions attributed to this local RAS are maintenance of seminal plasma electrolytes, regulation of steroidogenesis and spermatogenesis, and sperm functions. However, their specific actions in these locations are not fully understood. Therefore, a deep knowledge of the functions of the RAS at both the testicular and seminal levels could clarify its roles in male infertility and sperm physiology, and the different RAS elements could be used to design tools enabling the diagnosis and/or treatment of male infertility.
Topics: Humans; Infertility, Male; Male; Renin-Angiotensin System; Semen; Spermatogenesis; Spermatozoa; Testis
PubMed: 33114706
DOI: 10.3390/ijms21217943 -
Physiological Reviews Apr 2021Fibroblast growth factors (FGFs) are a family of proteins possessing paracrine, autocrine, or endocrine functions in a variety of biological processes, including... (Review)
Review
Fibroblast growth factors (FGFs) are a family of proteins possessing paracrine, autocrine, or endocrine functions in a variety of biological processes, including embryonic development, angiogenesis, tissue homeostasis, wound repair, and cancer. Canonical FGFs bind and activate tyrosine kinase FGF receptors (FGFRs), triggering intracellular signaling cascades that mediate their biological activity. Experimental evidence indicates that FGFs play a complex role in the physiopathology of the prostate gland that ranges from essential functions during embryonic development to modulation of neoplastic transformation. The use of ligand- and receptor-deleted mouse models has highlighted the requirement for FGF signaling in the normal development of the prostate gland. In adult prostate, the maintenance of a functional FGF/FGFR signaling axis is critical for organ homeostasis and function, as its disruption leads to prostate hyperplasia and may contribute to cancer progression and metastatic dissemination. Dissection of the molecular landscape modulated by the FGF family will facilitate ongoing translational efforts directed toward prostate cancer therapy.
Topics: Animals; Fibroblast Growth Factors; Humans; Intercellular Signaling Peptides and Proteins; Male; Prostate; Prostatic Diseases; Prostatic Neoplasms; Receptors, Fibroblast Growth Factor
PubMed: 32730114
DOI: 10.1152/physrev.00005.2020 -
American Journal of Physiology. Cell... Feb 2023Activins and inhibins are unique members of the transforming growth factor-β (TGFβ) family of growth factors, with the ability to exert autocrine, endocrine, and... (Review)
Review
Activins and inhibins are unique members of the transforming growth factor-β (TGFβ) family of growth factors, with the ability to exert autocrine, endocrine, and paracrine effects in a wide range of complex physiologic and pathologic processes. Although first isolated within the pituitary, emerging evidence suggests broader influence beyond reproductive development and function. Known roles of activin and inhibin in angiogenesis and immunity along with correlations between gene expression and cancer prognosis suggest potential roles in tumorigenesis. Here, we present a review of the current understanding of the biological role of activins and inhibins as it relates to ovarian cancers, summarizing the underlying signaling mechanisms and physiologic influence, followed by detailing their roles in cancer progression, diagnosis, and treatment.
Topics: Humans; Female; Inhibins; Activins; Ovarian Neoplasms; Signal Transduction; Endocrine System
PubMed: 36622068
DOI: 10.1152/ajpcell.00178.2022 -
Cancers Sep 2021Pancreatic ductal adenocarcinoma (PDAC) is one of the cancers with the highest incidence of perineural invasion (PNI), which often indicates a poor prognosis. Aggressive... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) is one of the cancers with the highest incidence of perineural invasion (PNI), which often indicates a poor prognosis. Aggressive tumor cells invade nerves, causing neurogenic inflammation; the tumor microenvironment also induces nerves to undergo a series of structural and functional reprogramming. In turn, neurons and the surrounding glial cells promote the development of pancreatic cancer through autocrine and/or paracrine signaling. In addition, hyperalgesia in PDAC patients implies alterations of pain transmission in the peripheral and central nervous systems. Currently, the studies on this topic are relatively limited. This review will elaborate on the mechanisms of tumor-neural interactions and its possible relationship with pain from several aspects that have been focused on in recent years.
PubMed: 34572820
DOI: 10.3390/cancers13184594 -
Frontiers in Endocrinology 2021Somatostatin (SST) and somatostatin receptors (SSTRs) play an important role in the brain and gastrointestinal (GI) system. SST is produced in various organs and cells,... (Review)
Review
Somatostatin (SST) and somatostatin receptors (SSTRs) play an important role in the brain and gastrointestinal (GI) system. SST is produced in various organs and cells, and the inhibitory function of somatostatin-containing cells is involved in a range of physiological functions and pathological modifications. The GI system is the largest endocrine organ for digestion and absorption, SST-endocrine cells and neurons in the GI system are a critical effecter to maintain homeostasis SSTRs 1-5 and co-receptors, while SST-SSTRs are involved in chemo-sensory, mucus, and hormone secretion, motility, inflammation response, itch, and pain the autocrine, paracrine, endocrine, and exoendocrine pathways. It is also a power inhibitor for tumor cell proliferation, severe inflammation, and post-operation complications, and is a first-line anti-cancer drug in clinical practice. This mini review focuses on the current function of producing SST endocrine cells and local neurons SST-SSTRs in the GI system, discusses new development prognostic markers, phosphate-specific antibodies, and molecular imaging emerging in diagnostics and therapy, and summarizes the mechanism of the SST family in basic research and clinical practice. Understanding of endocrines and neuroendocrines in SST-SSTRs in GI will provide an insight into advanced medicine in basic and clinical research.
Topics: Animals; Antineoplastic Agents; Cell Communication; Cell Proliferation; Disease Models, Animal; Enteric Nervous System; Gastrointestinal Tract; Homeostasis; Humans; Inflammation; Ligands; Neurons; Parasympathetic Nervous System; Prognosis; Receptors, Somatostatin; Somatostatin; Somatostatin-Secreting Cells; Sympathetic Nervous System
PubMed: 33796080
DOI: 10.3389/fendo.2021.652363 -
Frontiers in Immunology 2019The bone matrix is constantly remodeled by bone-resorbing osteoclasts and bone-forming osteoblasts. These two cell types are fundamentally different in terms of... (Review)
Review
The bone matrix is constantly remodeled by bone-resorbing osteoclasts and bone-forming osteoblasts. These two cell types are fundamentally different in terms of progenitor cells, mode of action and regulation by specific molecules, acting either systemically or locally. Importantly, there is increasing evidence for an impact of cell types or molecules of the adaptive and innate immune system on bone remodeling. Understanding these influences is the major goal of a novel research area termed osteoimmunology, which is of key relevance in the context of inflammation-induced bone loss, skeletal metastases, and diseases of impaired bone remodeling, such as osteoporosis. This review article aims at summarizing the current knowledge on one particular aspect of osteoimmunology, namely the impact of chemokines on skeletal cells in order to regulate bone remodeling under physiological and pathological conditions. Chemokines have key roles in the adaptive immune system by controlling migration, localization, and function of immune cells during inflammation. The vast majority of chemokines are divided into two subgroups based on the pattern of cysteine residues. More specifically, there are 27 known C-C-chemokines, binding to 10 different C-C receptors, and 17 known C-X-C-chemokines binding to seven different C-X-C receptors. Three additional chemokines do not fall into this category, and only one of them, i.e., CX3CL1, has been shown to influence bone remodeling cell types. There is a large amount of published studies demonstrating specific effects of certain chemokines on differentiation and function of osteoclasts and/or osteoblasts. Chemokine signaling by skeletal cells or by other cells of the bone marrow niche regulates bone formation and resorption through autocrine and paracrine mechanisms. evidence from mouse deficiency models strongly supports the role of certain chemokine signaling pathways in bone remodeling. We will summarize these data in the present review with a special focus on the most established subsets of chemokines. In combination with the other review articles of this issue, the knowledge presented here confirms that there is a physiologically relevant crosstalk between the innate immune system and bone remodeling cell types, whose molecular understanding is of high clinical relevance.
Topics: Animals; Bone Resorption; Chemokines; Humans; Mice; Osteoblasts; Osteoclasts; Osteogenesis; Signal Transduction
PubMed: 31572390
DOI: 10.3389/fimmu.2019.02182 -
Current Opinion in Endocrine and... Dec 2022The pulsatile release of gonadotropin-releasing hormone (GnRH) and its frequency are crucial for healthy reproductive function. To understand what drives GnRH pulses, a... (Review)
Review
The pulsatile release of gonadotropin-releasing hormone (GnRH) and its frequency are crucial for healthy reproductive function. To understand what drives GnRH pulses, a combination of experimental and mathematical modelling approaches has been used. Early work focussed on the possibility that GnRH pulse generation is an intrinsic feature of GnRH neurons, with autocrine feedback generating pulsatility. However, there is now ample evidence suggesting that a network of upstream neurons secreting kisspeptin, neurokinin-B and dynorphin are the source of this GnRH pulse generator. The interplay of slow positive and negative feedback via neurokinin-B and dynorphin, respectively, allows the network to act as a relaxation oscillator, driving pulsatile secretion of kisspeptin, and consequently, of GnRH and LH. Here, we review the mathematical modelling approaches exploring both scenarios and suggest that with pulsatile GnRH secretion driven by the KNDy pulse generator, autocrine feedback still has the potential to modulate GnRH output.
PubMed: 36632147
DOI: 10.1016/j.coemr.2022.100407 -
Frontiers in Cell and Developmental... 2022A primary reason behind the high level of complexity we embody as multicellular organisms is a highly complex intracellular and intercellular communication system. As a... (Review)
Review
A primary reason behind the high level of complexity we embody as multicellular organisms is a highly complex intracellular and intercellular communication system. As a result, the activities of multiple cell types and tissues can be modulated resulting in a specific physiological function. One of the key players in this communication process is extracellular signaling molecules that can act in autocrine, paracrine, and endocrine fashion to regulate distinct physiological responses. Neurotransmitters and neuropeptides are signaling molecules that renders long-range communication possible. In normal conditions, neurotransmitters are involved in normal responses such as development and normal physiological aspects; however, the dysregulation of neurotransmitters mediated signaling has been associated with several pathologies such as neurodegenerative, neurological, psychiatric disorders, and other pathologies. One of the interesting topics that is not yet fully explored is the connection between neuronal signaling and physiological changes during oocyte maturation and fertilization. Knowing the importance of Ca signaling in these reproductive processes, our objective in this review is to highlight the link between the neuronal signals and the intracellular changes in calcium during oocyte maturation and embryogenesis. Calcium (Ca) is a ubiquitous intracellular mediator involved in various cellular functions such as releasing neurotransmitters from neurons, contraction of muscle cells, fertilization, and cell differentiation and morphogenesis. The multiple roles played by this ion in mediating signals can be primarily explained by its spatiotemporal dynamics that are kept tightly checked by mechanisms that control its entry through plasma membrane and its storage on intracellular stores. Given the large electrochemical gradient of the ion across the plasma membrane and intracellular stores, signals that can modulate Ca entry channels or Ca receptors in the stores will cause Ca to be elevated in the cytosol and consequently activating downstream Ca-responsive proteins resulting in specific cellular responses. This review aims to provide an overview of the reported neurotransmitters and neuropeptides that participate in early stages of development and their association with Ca signaling.
PubMed: 36211465
DOI: 10.3389/fcell.2022.980219 -
Nature Communications Dec 2023Insulin secretion from pancreatic β cells is regulated by multiple stimuli, including nutrients, hormones, neuronal inputs, and local signalling. Amino acids modulate...
Insulin secretion from pancreatic β cells is regulated by multiple stimuli, including nutrients, hormones, neuronal inputs, and local signalling. Amino acids modulate insulin secretion via amino acid transporters expressed on β cells. The granin protein VGF has dual roles in β cells: regulating secretory granule formation and functioning as a multiple peptide precursor. A VGF-derived peptide, neuroendocrine regulatory peptide-4 (NERP-4), increases Ca influx in the pancreata of transgenic mice expressing apoaequorin, a Ca-induced bioluminescent protein complex. NERP-4 enhances glucose-stimulated insulin secretion from isolated human and mouse islets and β-cell-derived MIN6-K8 cells. NERP-4 administration reverses the impairment of β-cell maintenance and function in db/db mice by enhancing mitochondrial function and reducing metabolic stress. NERP-4 acts on sodium-coupled neutral amino acid transporter 2 (SNAT2), thereby increasing glutamine, alanine, and proline uptake into β cells and stimulating insulin secretion. SNAT2 deletion and inhibition abolish the protective effects of NERP-4 on β-cell maintenance. These findings demonstrate a novel autocrine mechanism of β-cell maintenance and function that is mediated by the peptide-amino acid transporter axis.
Topics: Animals; Humans; Mice; Glucose; Insulin; Insulin Secretion; Insulin-Secreting Cells; Nerve Tissue Proteins; Neurosecretory Systems; Peptides; Amino Acid Transport System A
PubMed: 38071217
DOI: 10.1038/s41467-023-43976-8 -
Molecular & Cellular Proteomics : MCP Nov 2023Molecular clocks and daily feeding cycles support metabolism in peripheral tissues. Although the roles of local clocks and feeding are well defined at the...
Molecular clocks and daily feeding cycles support metabolism in peripheral tissues. Although the roles of local clocks and feeding are well defined at the transcriptional level, their impact on governing protein abundance in peripheral tissues is unclear. Here, we determine the relative contributions of local molecular clocks and daily feeding cycles on liver and muscle proteomes during the active phase in mice. LC-MS/MS was performed on liver and gastrocnemius muscle harvested 4 h into the dark phase from WT, Bmal1 KO, and dual liver- and muscle-Bmal1-rescued mice under either ad libitum feeding or time-restricted feeding during the dark phase. Feeding-fasting cycles had only minimal effects on levels of liver proteins and few, if any, on the muscle proteome. In contrast, Bmal1 KO altered the abundance of 674 proteins in liver and 80 proteins in muscle. Local rescue of liver and muscle Bmal1 restored ∼50% of proteins in liver and ∼25% in muscle. These included proteins involved in fatty acid oxidation in liver and carbohydrate metabolism in muscle. For liver, proteins involved in de novo lipogenesis were largely dependent on Bmal1 function in other tissues (i.e., the wider clock system). Proteins regulated by BMAL1 in liver and muscle were enriched for secreted proteins. We found that the abundance of fibroblast growth factor 1, a liver secreted protein, requires BMAL1 and that autocrine fibroblast growth factor 1 signaling modulates mitochondrial respiration in hepatocytes. In liver and muscle, BMAL1 is a more potent regulator of dark phase proteomes than daily feeding cycles, highlighting the need to assess protein levels in addition to mRNA when investigating clock mechanisms. The proteome is more extensively regulated by BMAL1 in liver than in muscle, and many metabolic pathways in peripheral tissues are reliant on the function of the clock system as a whole.
Topics: Animals; Mice; ARNTL Transcription Factors; Chromatography, Liquid; Circadian Clocks; Circadian Rhythm; Fibroblast Growth Factor 1; Liver; Muscles; Proteome; Tandem Mass Spectrometry
PubMed: 37793502
DOI: 10.1016/j.mcpro.2023.100655