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Molecular and Cellular Endocrinology Jun 2012Steroid hormones coordinate and control the development and function of many organs and are implicated in many pathological processes. Progesterone signaling, in... (Review)
Review
Steroid hormones coordinate and control the development and function of many organs and are implicated in many pathological processes. Progesterone signaling, in particular, is essential for several important female reproductive functions. Physiological effects of progesterone are mediated by its cognate receptor, expressed in a subset of cells in target tissues. Experimental evidence has accumulated that progesterone acts through both cell intrinsic as well as paracrine signaling mechanisms. By relegating the hormonal stimulus to paracrine signaling cascades the systemic signal gets amplified locally and signaling reaches different cell types that are devoid of hormone receptors. Interestingly, distinct biological responses to progesterone in different target tissues rely on several tissue-specific and some common paracrine factors that coordinate biological responses in different cell types. Evidence is forthcoming that the intercellular signaling pathways that control development and physiological functions are important in tumorigenesis.
Topics: Animals; Female; Humans; Paracrine Communication; Progesterone; Progestins; Signal Transduction
PubMed: 21945477
DOI: 10.1016/j.mce.2011.09.018 -
Expert Review of Cardiovascular Therapy 2016Myofibroblasts (myoFb) are phenotypically transformed, contractile fibroblast-like cells expressing α-smooth muscle actin microfilaments. They are integral to collagen... (Review)
Review
Myofibroblasts (myoFb) are phenotypically transformed, contractile fibroblast-like cells expressing α-smooth muscle actin microfilaments. They are integral to collagen fibrillogenesis with scar tissue formation at sites of repair irrespective of the etiologic origins of injury or tissue involved. MyoFb can persist long after healing is complete, where their ongoing turnover of collagen accounts for a progressive structural remodeling of an organ (a.k.a. fibrosis, sclerosis or cirrhosis). Such persistent metabolic activity is derived from a secretome consisting of requisite components in the de novo generation of angiotensin (Ang) II. Autocrine and paracrine signaling induced by tissue AngII is expressed via AT1 receptor ligand binding to respectively promote: i) regulation of myoFb collagen synthesis via the fibrogenic cytokine TGF-β1-Smad pathway; and ii) dedifferentiation and protein degradation of atrophic myocytes immobilized and ensnared by fibrillar collagen at sites of scarring. Several cardioprotective strategies in the prevention of fibrosis and involving myofibroblasts are considered. They include: inducing myoFb apoptosis through inactivation of antiapoptotic proteins; AT1 receptor antagonist to interfere with auto-/paracrine myoFb signaling or to induce counterregulatory expression of ACE2; and attacking the AngII-AT1R-TGF-β1-Smad pathway by antibody or the use of triplex-forming oligonucleotides.
Topics: Angiotensin II; Collagen; Fibroblasts; Fibrosis; Humans; Myofibroblasts; Paracrine Communication; Wound Healing
PubMed: 26818589
DOI: 10.1586/14779072.2016.1147348 -
Physiology (Bethesda, Md.) Oct 2007The aspartyl-protease renin is the key regulator of the renin-angiotensin-aldosterone system, which is critically involved in salt, volume, and blood pressure... (Review)
Review
The aspartyl-protease renin is the key regulator of the renin-angiotensin-aldosterone system, which is critically involved in salt, volume, and blood pressure homeostasis of the body. Renin is mainly produced and released into circulation by the so-called juxtaglomerular epithelioid cells, located in the walls of renal afferent arterioles at the entrance of the glomerular capillary network. It has been known for a long time that renin synthesis and secretion are stimulated by the sympathetic nerves and the prostaglandins and are inhibited in negative feedback loops by angiotensin II, high blood pressure, salt, and volume overload. In contrast, the events controlling the function of renin-secreting cells at the organ and cellular level are markedly less clear and remain mysterious in certain aspects. The unravelling of these mysteries has led to new and interesting insights into the process of renin release.
Topics: Animals; Cyclic AMP; Humans; Juxtaglomerular Apparatus; Kidney; Paracrine Communication; Protein Processing, Post-Translational; Renin; Secretory Vesicles; Signal Transduction
PubMed: 17928544
DOI: 10.1152/physiol.00024.2007 -
Biomolecules May 2021Organ fibrosis is a common pathological result of various chronic diseases with multiple causes. Fibrosis is characterized by the excessive deposition of extracellular... (Review)
Review
Organ fibrosis is a common pathological result of various chronic diseases with multiple causes. Fibrosis is characterized by the excessive deposition of extracellular matrix and eventually leads to the destruction of the tissue structure and impaired organ function. Prostaglandins are produced by arachidonic acid through cyclooxygenases and various prostaglandin-specific synthases. Prostaglandins bind to homologous receptors on adjacent tissue cells in an autocrine or paracrine manner and participate in the regulation of a series of physiological or pathological processes, including fibrosis. This review summarizes the properties, synthesis, and degradation of various prostaglandins, as well as the roles of these prostaglandins and their receptors in fibrosis in multiple models to reveal the clinical significance of prostaglandins and their receptors in the treatment of fibrosis.
Topics: Animals; Autocrine Communication; Chronic Disease; Fibrosis; Humans; Paracrine Communication; Prostaglandin-Endoperoxide Synthases; Prostaglandins
PubMed: 34073892
DOI: 10.3390/biom11060789 -
Physiological Reviews Jul 2020Autocrine and paracrine signaling in the kidney adds an extra level of diversity and complexity to renal physiology. The extensive scientific production on the topic... (Review)
Review
Autocrine and paracrine signaling in the kidney adds an extra level of diversity and complexity to renal physiology. The extensive scientific production on the topic precludes easy understanding of the fundamental purpose of the vast number of molecules and systems that influence the renal function. This systematic review provides the broader pen strokes for a collected image of renal paracrine signaling. First, we recapitulate the essence of each paracrine system one by one. Thereafter the single components are merged into an overarching physiological concept. The presented survey shows that despite the diversity in the web of paracrine factors, the collected effect on renal function may not be complicated after all. In essence, paracrine activation provides an intelligent system that perceives minor perturbations and reacts with a coordinated and integrated tissue response that relieves the work load from the renal epithelia and favors diuresis and natriuresis. We suggest that the overall function of paracrine signaling is reno-protection and argue that renal paracrine signaling and self-regulation are two sides of the same coin. Thus local paracrine signaling is an intrinsic function of the kidney, and the overall renal effect of changes in blood pressure, volume load, and systemic hormones will always be tinted by its paracrine status.
Topics: Animals; Autocrine Communication; Humans; Kidney; Paracrine Communication; Signal Transduction
PubMed: 31999508
DOI: 10.1152/physrev.00014.2019 -
Circulation Research Jan 2018Cardiac excitation-contraction coupling (ECC) is the orchestrated process of initial myocyte electrical excitation, which leads to calcium entry, intracellular... (Review)
Review
Cardiac excitation-contraction coupling (ECC) is the orchestrated process of initial myocyte electrical excitation, which leads to calcium entry, intracellular trafficking, and subsequent sarcomere shortening and myofibrillar contraction. Neurohumoral β-adrenergic signaling is a well-established mediator of ECC; other signaling mechanisms, such as paracrine signaling, have also demonstrated significant impact on ECC but are less well understood. For example, resident heart endothelial cells are well-known physiological paracrine modulators of cardiac myocyte ECC mainly via NO and endothelin-1. Moreover, recent studies have demonstrated other resident noncardiomyocyte heart cells (eg, physiological fibroblasts and pathological myofibroblasts), and even experimental cardiotherapeutic cells (eg, mesenchymal stem cells) are also capable of altering cardiomyocyte ECC through paracrine mechanisms. In this review, we first focus on the paracrine-mediated effects of resident and therapeutic noncardiomyocytes on cardiomyocyte hypertrophy, electrophysiology, and calcium handling, each of which can modulate ECC, and then discuss the current knowledge about key paracrine factors and their underlying mechanisms of action. Next, we provide a case example demonstrating the promise of tissue-engineering approaches to study paracrine effects on tissue-level contractility. More specifically, we present new functional and molecular data on the effects of human adult cardiac fibroblast conditioned media on human engineered cardiac tissue contractility and ion channel gene expression that generally agrees with previous murine studies but also suggests possible species-specific differences. By contrast, paracrine secretions by human dermal fibroblasts had no discernible effect on human engineered cardiac tissue contractile function and gene expression. Finally, we discuss systems biology approaches to help identify key stem cell paracrine mediators of ECC and their associated mechanistic pathways. Such integration of tissue-engineering and systems biology methods shows promise to reveal novel insights into paracrine mediators of ECC and their underlying mechanisms of action, ultimately leading to improved cell-based therapies for patients with heart disease.
Topics: Animals; Cells, Cultured; Excitation Contraction Coupling; Fibroblasts; Humans; Mesenchymal Stem Cells; Myocardial Contraction; Myocytes, Cardiac; Paracrine Communication
PubMed: 29301848
DOI: 10.1161/CIRCRESAHA.117.311589 -
Cell Death and Differentiation Mar 2019In mammalian cells, autophagy is the major pathway for the degradation and recycling of obsolete and potentially noxious cytoplasmic materials, including proteins,... (Review)
Review
In mammalian cells, autophagy is the major pathway for the degradation and recycling of obsolete and potentially noxious cytoplasmic materials, including proteins, lipids, and whole organelles, through the lysosomes. Autophagy maintains cellular and tissue homeostasis and provides a mechanism to adapt to extracellular cues and metabolic stressors. Emerging evidence unravels a critical function of autophagy in endothelial cells (ECs), the major components of the blood vasculature, which delivers nutrients and oxygen to the parenchymal tissue. EC-intrinsic autophagy modulates the response of ECs to various metabolic stressors and has a fundamental role in redox homeostasis and EC plasticity. In recent years moreover, genetic evidence suggests that autophagy regulates pathological angiogenesis, a hallmark of solid tumors. In the hypoxic, nutrient-deprived, and pro-angiogenic tumor microenvironment, heightened autophagy in the blood vessels is emerging as a critical mechanism enabling ECs to dynamically accommodate their higher bioenergetics demands to the extracellular environment and connect with other components of the tumor stroma through paracrine signaling. In this review, we provide an overview of the major cellular mechanisms regulated by autophagy in ECs and discuss their potential role in tumor angiogenesis, tumor growth, and response to anticancer therapy.
Topics: Animals; Autophagy; Endothelial Cells; Endothelium, Vascular; Homeostasis; Humans; Lipid Metabolism; Lysosomes; Neoplasms; Neovascularization, Pathologic; Oxidation-Reduction; Paracrine Communication; Signal Transduction; Tumor Microenvironment
PubMed: 30692642
DOI: 10.1038/s41418-019-0287-8 -
American Journal of Physiology.... Jan 2021Insulin secretion by β-cells is largely controlled by circulating nutrients, hormones, and neurotransmitters. However, recent years have witnessed the multiplication of... (Review)
Review
Insulin secretion by β-cells is largely controlled by circulating nutrients, hormones, and neurotransmitters. However, recent years have witnessed the multiplication of studies investigating whether local regulation also takes place within pancreatic islets, in which β-cells cohabit with several other cell types. The cell composition and architectural organization of human islets differ from those of rodent islets and are particularly favorable to cellular interactions. An impressive number of hormonal (glucagon, glucagon-like peptide-1, somatostatin, etc.) and nonhormonal products (ATP, acetylcholine, γ-aminobutyric acid, dopamine, etc.) are released by islet cells and have been implicated in a local control of insulin secretion. This review analyzes reports directly testing paracrine and autocrine control of insulin secretion in isolated human islets. Many of these studies were designed on background information collected in rodent islets. However, the perspective of the review is not to highlight species similarities or specificities but to contrast established and speculative mechanisms in human islets. It will be shown that the current evidence is convincing only for a minority of candidates for a paracrine function whereas arguments supporting a physiological role of others do not stand up to scrutiny. Several pending questions await further investigation.
Topics: Autocrine Communication; Hormones; Humans; Insulin Secretion; Islets of Langerhans; Paracrine Communication
PubMed: 33103455
DOI: 10.1152/ajpendo.00485.2020 -
Purinergic Signalling Sep 2021Cancer comprises a collection of diseases that occur in almost any tissue and it is characterized by an abnormal and uncontrolled cell growth that results in tumor... (Review)
Review
Cancer comprises a collection of diseases that occur in almost any tissue and it is characterized by an abnormal and uncontrolled cell growth that results in tumor formation and propagation to other tissues, causing tissue and organ malfunction and death. Despite the undeniable improvement in cancer diagnostics and therapy, there is an urgent need for new therapeutic and preventive strategies with improved efficacy and fewer side effects. In this context, purinergic signaling emerges as an interesting candidate as a cancer biomarker or therapeutic target. There is abundant evidence that tumor cells have significant changes in the expression of purinergic receptors, which comprise the G-protein coupled P2Y and AdoR families of receptors and the ligand-gated ion channel P2X receptors. Tumor cells also exhibit changes in the expression of nucleotidases and other enzymes involved in nucleotide metabolism, and the concentrations of extracellular nucleotides are significantly higher than those observed in normal cells. In this review, we will focus on the potential role of purinergic signaling in the ten most lethal cancers (lung, breast, colorectal, liver, stomach, prostate, cervical, esophagus, pancreas, and ovary), which together are responsible for more than 5 million annual deaths.
Topics: Adenosine Triphosphate; Animals; Autocrine Communication; Humans; Neoplasms; Paracrine Communication; Receptors, Purinergic; Signal Transduction
PubMed: 33982134
DOI: 10.1007/s11302-021-09785-8 -
Genesis (New York, N.Y. : 2000) Apr 2011The formation and invagination of the optic stalk coincides with the migration of cranial neural crest (CNC) cells, and a growing body of data reveals that the optic... (Review)
Review
The formation and invagination of the optic stalk coincides with the migration of cranial neural crest (CNC) cells, and a growing body of data reveals that the optic stalk and CNC cells communicate to lay the foundations for periocular and craniofacial development. Following migration, the interaction between the developing eye and surrounding periocular mesenchyme (POM) continues, leading to induction of transcriptional regulatory cascades that regulate craniofacial morphogenesis. Studies in chick, mice, and zebrafish have revealed a remarkable level of genetic and mechanistic conservation, affirming the power of each animal model to shed light on the broader morphogenic process. This review will focus on the role of the developing eye in orchestrating craniofacial morphogenesis, utilizing morphogenic gradients, paracrine signaling, and transcriptional regulatory cascades to establish an evolutionarily-conserved facial architecture. We propose that in addition to the forebrain, the eye functions during early craniofacial morphogenesis as a key organizer of facial development, independent of its role in vision.
Topics: Animals; Biological Evolution; Cell Movement; Eye; Gene Expression Regulation, Developmental; Homeodomain Proteins; Humans; Maxillofacial Development; Morphogenesis; Neural Crest; Paracrine Communication; Skull; Transcription Factors; Homeobox Protein PITX2
PubMed: 21309065
DOI: 10.1002/dvg.20716