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Hormone Research in Paediatrics 2019McCune-Albright syndrome (MAS) is a rare, mosaic disorder presenting along a broad clinical spectrum. Disease arises from somatic-activating GNAS mutations, leading to... (Review)
Review
McCune-Albright syndrome (MAS) is a rare, mosaic disorder presenting along a broad clinical spectrum. Disease arises from somatic-activating GNAS mutations, leading to constitutive Gαs activation and ligand-independent signaling of the Gαs-coupled protein receptor. The phenotype is largely determined by location and extent of tissues in which the GNAS mutation is expressed, as well as the pathophysiologic effects of Gαs activation within these tissues. Patients pre-sent clinically with a variable combination of fibrous dysplasia of bone (FD), café-au-lait skin macules, and hyperfunctioning endocrinopathies. In bone, Gαs leads to impaired differentiation of skeletal stem cells and formation of discrete, expansile FD lesions, resulting in fractures, pain, and functional impairment. A systematic approach to diagnosis and management is critically important to optimize outcomes for patients with FD/MAS. There are no medical therapies capable of altering the disease course in FD; however, screening and treatment for endocrinopathies can mitigate some skeletal morbidities. This review summarizes current understanding of MAS pathophysiology, describes the spectrum of clinical features, and includes a detailed discussion of the recommended approach to diagnosis and management.
Topics: Chromogranins; Fibrous Dysplasia, Polyostotic; GTP-Binding Protein alpha Subunits, Gs; Humans; Mutation
PubMed: 31865341
DOI: 10.1159/000504802 -
International Journal of Molecular... Feb 2024Preeclampsia (PE) is a unique pregnancy disorder affecting women across the world. It is characterized by the new onset of hypertension with coexisting end-organ damage.... (Review)
Review
Preeclampsia (PE) is a unique pregnancy disorder affecting women across the world. It is characterized by the new onset of hypertension with coexisting end-organ damage. Although the disease has been known for centuries, its exact pathophysiology and, most importantly, its prevention remain elusive. The basis of its associated molecular changes has been attributed to the placenta and the hormones regulating its function. One such hormone is chromogranin A (CgA). In the placenta, CgA is cleaved to form a variety of biologically active peptides, including catestatin (CST), known inter alia for its vasodilatory effects. Recent studies indicate that the CST protein level is diminished both in patients with hypertension and those with PE. Therefore, the aim of the present paper is to review the most recent and most relevant in vitro, in vivo, and clinical studies to provide an overview of the proposed impact of CST on the molecular processes of PE and to consider the possibilities for future experiments in this area.
Topics: Humans; Female; Chromogranin A; Pre-Eclampsia; Peptide Fragments; Hypertension
PubMed: 38473713
DOI: 10.3390/ijms25052461 -
Peptides Dec 2022Chromogranin A (CgA) is a 439 amino acid protein secreted by neuroendocrine cells. Proteolytic processing of CgA results in the production of different bioactive... (Review)
Review
Chromogranin A (CgA) is a 439 amino acid protein secreted by neuroendocrine cells. Proteolytic processing of CgA results in the production of different bioactive peptides. These peptides have been associated with inflammatory bowel disease, diabetes, and cancer. One of the chromogranin A-derived peptides is ∼52 amino acid long Pancreastatin (PST: human (h)CgA, murine (m)CgA). PST is a glycogenolytic peptide that inhibits glucose-induced insulin secretion from pancreatic islet β-cells. In addition to this metabolic role, evidence is emerging that PST also has inflammatory properties. This review will discuss the immunomodulatory properties of PST and its possible mechanisms of action and regulation. Moreover, this review will discuss the potential translation to humans and how PST may be an interesting therapeutic target for treating inflammatory diseases.
Topics: Humans; Animals; Mice; Chromogranin A; Pancreatic Hormones; Chromogranins; Peptides; Amino Acids
PubMed: 36244579
DOI: 10.1016/j.peptides.2022.170893 -
Trends in Immunology Jan 2022Catestatin (CST) is a bioactive cleavage product of the neuroendocrine prohormone chromogranin A (CgA). Recent findings show that CST can exert anti-inflammatory and... (Review)
Review
Catestatin (CST) is a bioactive cleavage product of the neuroendocrine prohormone chromogranin A (CgA). Recent findings show that CST can exert anti-inflammatory and antiadrenergic effects by suppressing the inflammatory actions of mammalian macrophages. However, recent findings also suggest that macrophages themselves are major CST producers. Here, we hypothesize that macrophages produce CST in an inflammation-dependent manner and thereby might self-regulate inflammation in an autocrine fashion. CST is associated with pathological conditions hallmarked by chronic inflammation, including autoimmune, cardiovascular, and metabolic disorders. Since intraperitoneal injection of CST in mouse models of diabetes and inflammatory bowel disease has been reported to be beneficial for mitigating disease, we posit that CST should be further investigated as a candidate target for treating certain inflammatory diseases.
Topics: Animals; Chromogranin A; Humans; Inflammation; Macrophages; Mammals; Mice; Peptide Fragments
PubMed: 34844850
DOI: 10.1016/j.it.2021.11.002 -
Bone Apr 2018GNAS is a complex imprinted gene encoding the alpha-subunit of the stimulatory heterotrimeric G protein (Gsα). GNAS gives rise to additional gene products that exhibit... (Review)
Review
GNAS is a complex imprinted gene encoding the alpha-subunit of the stimulatory heterotrimeric G protein (Gsα). GNAS gives rise to additional gene products that exhibit exclusively maternal or paternal expression, such as XLαs, a large variant of Gsα that shows exclusively paternal expression and is partly identical to the latter. Gsα itself is expressed biallelically in most tissues, although the expression occurs predominantly from the maternal allele in a small set of tissues, such as renal proximal tubules. Inactivating mutations in Gsα-coding GNAS exons are responsible for Albright's hereditary osteodystrophy (AHO), which refers to a constellation of physical and developmental disorders including obesity, short stature, brachydactyly, cognitive impairment, and heterotopic ossification. Patients with Gsα mutations can present with AHO in the presence or absence of end-organ resistance to multiple hormones including parathyroid hormone. Maternal Gsα mutations lead to AHO with hormone resistance (i.e. pseudohypoparathyroidism type-Ia), whereas paternal mutations cause AHO alone (i.e. pseudo-pseudohypoparathyroidism). Heterotopic ossification associated with AHO develops through intramembranous bone formation and is limited to dermis and subcutis. In rare cases carrying Gsα mutations, however, ossifications progress into deep connective tissue and skeletal muscle, a disorder termed progressive osseous heteroplasia (POH). Here I briefly review the genetic, clinical, and molecular aspects of these disorders caused by inactivating GNAS mutations, with particular emphasis on heterotopic ossification.
Topics: Animals; Chromogranins; Cyclic AMP; GTP-Binding Protein alpha Subunits, Gs; Humans; Mutation; Ossification, Heterotopic
PubMed: 28889026
DOI: 10.1016/j.bone.2017.09.002 -
International Journal of Molecular... Mar 2023Pregnancy is a state of physiological and hormonal changes. One of the endocrine factors involved in these processes is chromogranin A, an acidic protein produced, among... (Review)
Review
Pregnancy is a state of physiological and hormonal changes. One of the endocrine factors involved in these processes is chromogranin A, an acidic protein produced, among others, by the placenta. Although it has been previously linked to pregnancy, no existing articles have ever managed to clarify the role of this protein regarding this subject. Therefore, the aim of the present study is to gather knowledge of chromogranin A's function with reference to gestation and parturition, clarify elusive information, and, most importantly, to formulate hypotheses for the future studies to verify.
Topics: Pregnancy; Female; Humans; Chromogranin A; Chromogranins; Endocrine System; Parturition; Placenta; Peptide Fragments
PubMed: 36902417
DOI: 10.3390/ijms24054986 -
Endocrine Reviews Dec 2011The chromogranins (chromogranin A and chromogranin B), secretogranins (secretogranin II and secretogranin III), and additional related proteins (7B2, NESP55, proSAAS,... (Review)
Review
The chromogranins (chromogranin A and chromogranin B), secretogranins (secretogranin II and secretogranin III), and additional related proteins (7B2, NESP55, proSAAS, and VGF) that together comprise the granin family subserve essential roles in the regulated secretory pathway that is responsible for controlled delivery of peptides, hormones, neurotransmitters, and growth factors. Here we review the structure and function of granins and granin-derived peptides and expansive new genetic evidence, including recent single-nucleotide polymorphism mapping, genomic sequence comparisons, and analysis of transgenic and knockout mice, which together support an important and evolutionarily conserved role for these proteins in large dense-core vesicle biogenesis and regulated secretion. Recent data further indicate that their processed peptides function prominently in metabolic and glucose homeostasis, emotional behavior, pain pathways, and blood pressure modulation, suggesting future utility of granins and granin-derived peptides as novel disease biomarkers.
Topics: Animals; Biomarkers; Chromogranins; Endocrine Cells; GTP-Binding Protein alpha Subunits, Gs; Humans; Nerve Growth Factors; Neuroendocrine Cells; Neuroendocrine Secretory Protein 7B2; Neurons; Neuropeptides; Peptide Fragments; Secretory Vesicles; Sequence Homology, Amino Acid
PubMed: 21862681
DOI: 10.1210/er.2010-0027 -
Cellular and Molecular Life Sciences :... Feb 2018Secretogranin III (Scg3) is a member of the granin protein family that regulates the biogenesis of secretory granules. Scg3 was recently discovered as an angiogenic... (Review)
Review
Secretogranin III (Scg3) is a member of the granin protein family that regulates the biogenesis of secretory granules. Scg3 was recently discovered as an angiogenic factor, expanding its functional role to extrinsic regulation. Unlike many other known angiogenic factors, the pro-angiogenic actions of Scg3 are restricted to pathological conditions. Among thousands of quantified endothelial ligands, Scg3 has the highest binding activity ratio to diabetic vs. healthy mouse retinas and lowest background binding to normal vessels. In contrast, vascular endothelial growth factor binds to and stimulates angiogenesis of both diabetic and control vasculature. Consistent with its role in pathological angiogenesis, Scg3-neutralizing antibodies alleviate retinal vascular leakage in mouse models of diabetic retinopathy and retinal neovascularization in oxygen-induced retinopathy mice. This review summarizes our current knowledge of Scg3 as a regulatory protein of secretory granules, highlights its new role as a highly disease-selective angiogenic factor, and envisions Scg3 inhibitors as "selective angiogenesis blockers" for targeted therapy.
Topics: Angiogenesis Inducing Agents; Animals; Chromogranins; Diabetic Retinopathy; Humans; Mice; Neovascularization, Pathologic; Retinal Vessels; Secretory Vesicles
PubMed: 28856381
DOI: 10.1007/s00018-017-2635-5 -
Diagnostic Pathology Nov 2022Synaptophysin is an immunohistochemical marker for neuroendocrine differentiation and is widely used in pathologic diagnosis. Its expression in malignant lymphoma has...
BACKGROUND
Synaptophysin is an immunohistochemical marker for neuroendocrine differentiation and is widely used in pathologic diagnosis. Its expression in malignant lymphoma has not yet been described. However, we experienced an index case of classic Hodgkin lymphoma with synaptophysin expression. This experience prompted us to investigate synaptophysin expression in classic Hodgkin lymphoma.
METHOD
Immunohistochemical staining of synaptophysin was performed in 59 diagnosed cases of classic Hodgkin lymphoma, 10 anaplastic large cell lymphomas, 16 diffuse large B-cell lymphomas, and 5 extranodal marginal zone lymphoma of the mucosa-associated tissue. Synaptophysin-positive cases were stained for both chromogranin and CD56a.
RESULT
Of 59 classic Hodgkin lymphoma cases, 11 (19%) were positive for synaptophysin. None of the anaplastic large cell lymphomas expressed synaptophysin. Synaptophysin showed weak but specific expression in the cytoplasm of the Hodgkin lymphoma tumor cells. Other background inflammatory cells (such as macrophages, B-, and T-lymphocytes) were all negative for synaptophysin expression. Chromogranin and CD56a were not expressed in the synaptophysin-positive classic Hodgkin lymphomas.
CONCLUSIONS
Synaptophysin is an integral glycoprotein present in presynaptic vesicles of neurons and neuroendocrine cells. It is a diagnostic marker for neuroendocrine tumors. Aberrant synaptophysin expression has been reported in non-neuroendocrine tumors but not in lymphoma or leukemia. To the best of our knowledge, synaptophysin positivity has only been reported in a single case of precursor T-lymphoblastic leukemia/lymphoma to date. Our study showed that aberrant synaptophysin expression in classic Hodgkin lymphoma is an unexpectedly frequent finding. The mechanism underlying, and prognostic significance of, such aberrant expression is unclear. Thus, in a small biopsy, aberrant synaptophysin expression could be a diagnostic pitfall and should be carefully avoided.
Topics: Humans; Hodgkin Disease; Synaptophysin; Immunohistochemistry; Chromogranins; Lymphoma, Large-Cell, Anaplastic; Lymphoma, Large B-Cell, Diffuse; Neuroendocrine Tumors
PubMed: 36401284
DOI: 10.1186/s13000-022-01272-x -
The Yale Journal of Biology and Medicine 1998ECL cells produce histamine and chromogranin A, and are restricted to the oxyntic mucosa of the stomach. ECL cell ontogeny has been studied in some detail in the rat.... (Review)
Review
ECL cells produce histamine and chromogranin A, and are restricted to the oxyntic mucosa of the stomach. ECL cell ontogeny has been studied in some detail in the rat. Using histidine decarboxylase immunostaining, the first ECL cells can be demonstrated at embryonic day 17. Immunoreactive histamine and chromogranin A appear one day later. At embryonic day 20, the vesicular monoamine transporter type 2 is also present in the ECL cells. Neonatally the ECL cell proliferation is slow; however, one to three weeks postnatally there is a rapid growth of ECL cells to populate the basal half of the glands. Gastrin is known to be an important stimulator of ECL cell activity and growth in the adult rat. As revealed in recent mouse gene knock out models gastrin does not seem to play a role in the early ECL cell differentiation and development.
Topics: Animals; Chromogranin A; Chromogranins; Enterochromaffin-like Cells; Gastrins; Histamine; Histidine Decarboxylase; Humans; Membrane Glycoproteins; Membrane Transport Proteins; Mice; Neuropeptides; Rats; Stomach; Vesicular Biogenic Amine Transport Proteins; Vesicular Monoamine Transport Proteins
PubMed: 10461348
DOI: No ID Found