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BMC Biology Dec 2022Decidualization refers to the process of transformation of endometrial stromal fibroblast cells into specialized decidual stromal cells that provide a nutritive and...
BACKGROUND
Decidualization refers to the process of transformation of endometrial stromal fibroblast cells into specialized decidual stromal cells that provide a nutritive and immunoprivileged matrix essential for blastocyst implantation and placental development. Deficiencies in decidualization are associated with a variety of pregnancy disorders, including female infertility, recurrent implantation failure (RIF), and miscarriages. Despite the increasing number of genes reportedly associated with endometrial receptivity and decidualization, the cellular and molecular mechanisms triggering and underlying decidualization remain largely unknown. Here, we analyze single-cell transcriptional profiles of endometrial cells during the window of implantation and decidual cells of early pregnancy, to gains insights on the process of decidualization.
RESULTS
We observed a unique IGF1 stromal cell that may initiate decidualization by single-cell RNA sequencing. We found the IL1B stromal cells promote gland degeneration and decidua hemostasis. We defined a subset of NK cells for accelerating decidualization and extravillous trophoblast (EVT) invasion by AREG-IGF1 and AREG-CSF1 regulatory axe. Further analysis indicates that EVT promote decidualization possibly by multiply pathways. Additionally, a systematic repository of cell-cell communication for decidualization was developed. An aberrant ratio conversion of IGF1 stromal cells to IGF1R stromal cells is observed in unexplained RIF patients.
CONCLUSIONS
Overall, a unique subpopulation of IGF1 stromal cell is involved in initiating decidualization. Our observations provide deeper insights into the molecular and cellular characterizations of decidualization, and a platform for further development of evaluation of decidualization degree and treatment for decidualization disorder-related diseases.
Topics: Pregnancy; Humans; Female; Placenta; Stromal Cells; Insulin-Like Growth Factor I
PubMed: 36482461
DOI: 10.1186/s12915-022-01483-0 -
International Journal of Molecular... Oct 2023This comprehensive review thoroughly explores the intricate involvement of insulin receptor (IR) isoforms and insulin-like growth factor receptors (IGFRs) in the context... (Review)
Review
This comprehensive review thoroughly explores the intricate involvement of insulin receptor (IR) isoforms and insulin-like growth factor receptors (IGFRs) in the context of the insulin and insulin-like growth factor (IGF) signaling (IIS) pathway. This elaborate system encompasses ligands, receptors, and binding proteins, giving rise to a wide array of functions, including aspects such as carcinogenesis and chemoresistance. Detailed genetic analysis of IR and IGFR structures highlights their distinct isoforms, which arise from alternative splicing and exhibit diverse affinities for ligands. Notably, the overexpression of the IR-A isoform is linked to cancer stemness, tumor development, and resistance to targeted therapies. Similarly, elevated IGFR expression accelerates tumor progression and fosters chemoresistance. The review underscores the intricate interplay between IRs and IGFRs, contributing to resistance against anti-IGFR drugs. Consequently, the dual targeting of both receptors could present a more effective strategy for surmounting chemoresistance. To conclude, this review brings to light the pivotal roles played by IRs and IGFRs in cellular signaling, carcinogenesis, and therapy resistance. By precisely modulating these receptors and their complex signaling pathways, the potential emerges for developing enhanced anti-cancer interventions, ultimately leading to improved patient outcomes.
Topics: Humans; Insulin; Receptor, Insulin; Drug Resistance, Neoplasm; Receptor, IGF Type 1; Signal Transduction; Protein Isoforms; Insulin, Regular, Human; Neoplasms; Somatomedins; Carcinogenesis; Insulin-Like Growth Factor I
PubMed: 37834454
DOI: 10.3390/ijms241915006 -
Biochemistry and Cell Biology =... Oct 2023Insulin-like growth factor-1 (IGF-1) is a critical modulator of cell growth and survival, making it a central part of maintaining essentially every biological system in... (Review)
Review
Insulin-like growth factor-1 (IGF-1) is a critical modulator of cell growth and survival, making it a central part of maintaining essentially every biological system in the body. Knowledge of the intricate mechanisms involved in activating IGF-1 signaling is not only key to understanding basic processes of growth and development, but also for addressing diseases, such as cancer and diabetes. This brief review explores how dysregulation of normal IGF-1 signaling can impact growth by examining its role in postnatal bone elongation. IGF-1 actions are dysregulated in autoimmune diseases, such as juvenile idiopathic arthritis and chronic kidney disease, which results in growth stunting. Conversely, childhood obesity results in growth acceleration, premature growth cessation, and ultimately, diminished bone quality, while systemic IGF-1 levels remain normal. Understanding the role of IGF-1 signaling in normal and dysregulated growth can add to other studies that address how this system regulates chronic diseases.
Topics: Child; Humans; Insulin-Like Growth Factor I; Chondrocytes; Growth Plate; Pediatric Obesity; Bone and Bones
PubMed: 37246759
DOI: 10.1139/bcb-2023-0025 -
Human adaptation to high altitude: a review of convergence between genomic and proteomic signatures.Human Genomics Jul 2022Both genomics- and proteomics-based investigations have identified several essential genes, proteins, and pathways that may facilitate human adaptive genotype/phenotype... (Review)
Review
Both genomics- and proteomics-based investigations have identified several essential genes, proteins, and pathways that may facilitate human adaptive genotype/phenotype in a population-specific manner. This comprehensive review provides an up-to-date list of genes and proteins identified for human adaptive responses to high altitudes. Genomics studies for indigenous high-altitude populations like Tibetans, Andeans, Ethiopians, and Sherpas have identified 169 genes under positive natural selection. Similarly, global proteomics studies have identified 258 proteins (± 1.2-fold or more) for Tibetan, Sherpa, and Ladakhi highlanders. The primary biological processes identified for genetic signatures include hypoxia-inducible factor (HIF)-mediated oxygen sensing, angiogenesis, and erythropoiesis. In contrast, major biological processes identified for proteomics signatures include 14-3-3 mediated sirtuin signaling, integrin-linked kinase (ILK), phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT), and integrin signaling. Comparing genetic and protein signatures, we identified 7 common genes/proteins (HBB/hemoglobin subunit beta, TF/serotransferrin, ANGPTL4/angiopoietin-related protein 4, CDC42/cell division control protein 42 homolog, GC/vitamin D-binding protein, IGFBP1/insulin-like growth factor-binding protein 1, and IGFBP2/insulin-like growth factor-binding protein 2) involved in crucial molecular functions like IGF-1 signaling, LXR/RXR activation, ferroptosis signaling, iron homeostasis signaling and regulation of cell cycle. Our combined multi-omics analysis identifies common molecular targets and pathways for human adaptation to high altitude. These observations further corroborate convergent positive selection of hypoxia-responsive molecular pathways in humans and advocate using multi-omics techniques for deciphering human adaptive responses to high altitude.
Topics: Altitude; Genomics; Humans; Hypoxia; Phosphatidylinositol 3-Kinases; Proteomics; Selection, Genetic; Somatomedins
PubMed: 35841113
DOI: 10.1186/s40246-022-00395-y -
Neuroscience and Biobehavioral Reviews Nov 2022Insulin-like growth factor-1 (IGF-1), a pleiotropic polypeptide, plays an essential role in CNS development and maturation. Glucagon-like peptide-1 (GLP-1) is an... (Review)
Review
Insulin-like growth factor-1 (IGF-1), a pleiotropic polypeptide, plays an essential role in CNS development and maturation. Glucagon-like peptide-1 (GLP-1) is an endogenous incretin hormone that regulates blood glucose levels and fatty acid oxidation in the brain. GLP-1 also exhibits similar functions and growth factor-like properties to IGF-1, which is likely how it exerts its neuroprotective effects. Recent preclinical and clinical evidence indicate that IGF-1 and GLP-1, apart from regulating growth and development, prevent neuronal death mediated by amyloidogenesis, cerebral glucose deprivation, neuroinflammation and apoptosis through modulation of PI3/Akt kinase, mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK/ERK). IGF-1 resistance and GLP-1 deficiency impair protective cellular signaling mechanisms, contributing to the progression of neurodegenerative diseases. Over the past decades, IGF-1 and GLP-1 have emerged as an essential component of the neuronal system and as potential therapeutic targets for several neurodegenerative and neuropsychiatric dysfunctions. There is substantial evidence that IGF-1 and GLP-1 analogues penetrate the blood-brain barrier (BBB) and exhibit neuroprotective functions, including synaptic formation, neuronal plasticity, protein synthesis, and autophagy. Conclusively, this review represents the therapeutic potential of IGF-1 and GLP-1 signaling target activators in ameliorating neurological disorders.
Topics: Humans; Glucagon-Like Peptide 1; Insulin-Like Growth Factor I; Signal Transduction; Neuroprotective Agents; Neuronal Plasticity
PubMed: 36191807
DOI: 10.1016/j.neubiorev.2022.104896 -
Animal Genetics Feb 2022Genomic imprinting occurs in therian mammals and is a phenomenon whereby the two alleles of a gene are differentially expressed, based on the sex of the parent from whom...
Genomic imprinting occurs in therian mammals and is a phenomenon whereby the two alleles of a gene are differentially expressed, based on the sex of the parent from whom the alleles were inherited. The allelic differences in expression are the consequence of different epigenetic modifications that are established in the sperm or oocyte during gametogenesis and transmitted at fertilization to offspring. A small minority of genes is regulated in this way but they have important biological functions, and aberrant regulation of imprinted genes contributes to disease aetiology in humans and other animals. The factors driving the evolution of imprinted genes are also of considerable interest, as these genes appear to forego the benefits of diploidy. To broaden the phylogenetic analysis of genomic imprinting, we began a study of imprinted genes in the domestic dog, Canis familiaris. In this report, we show that canine IGF2 and H19 are imprinted, with parent-of origin-dependent monoallelic expression patterns in neonatal umbilical cord. We identify a putative imprint control region associated with the genes, and provide evidence for differential methylation of this region in a somatic tissue (umbilical cord) and for its hypermethylation in the male germline. Canis familiaris is fast becoming a highly informative system for elucidating disease processes and evolution, and the study of imprinted genes in this species may help in understanding how these genes contribute to the generation of morphological and behavioral diversity.
Topics: Animals; DNA Methylation; Dogs; Genomic Imprinting; Insulin-Like Growth Factor II; Male; RNA, Long Noncoding
PubMed: 34676575
DOI: 10.1111/age.13148 -
Biochimica Et Biophysica Acta.... Nov 2019The insulin/insulin-like growth factor system (IIGFs) plays a fundamental role in the regulation of prenatal and postnatal growth, metabolism and homeostasis. As a... (Review)
Review
The insulin/insulin-like growth factor system (IIGFs) plays a fundamental role in the regulation of prenatal and postnatal growth, metabolism and homeostasis. As a consequence, dysregulation of this axis is associated with growth disturbance, type 2 diabetes, chronic inflammation and tumor progression. A functional crosstalk between IIGFs and discoidin domain receptors (DDRs) has been recently discovered. DDRs are non-integrin collagen receptors that canonically undergo slow and long-lasting autophosphorylation after binding to fibrillar collagen. While both DDR1 and DDR2 functionally interact with IIGFs, the crosstalk with DDR1 is so far better characterized. Notably, the IIGFs-DDR1 crosstalk presents a feed-forward mechanism, which does not require collagen binding, thus identifying novel non-canonical action of DDR1. Further studies are needed to fully explore the role of this IIGFs-DDRs functional loop as potential target in the treatment of inflammatory and neoplastic disorders.
Topics: Animals; Diabetes Mellitus, Type 2; Discoidin Domain Receptor 1; Discoidin Domain Receptor 2; Discoidin Domain Receptors; Fibrosis; Humans; Inflammation; Insulin; Insulin-Like Growth Factor II; Neoplasms; Phosphorylation; Protein Binding; Protein Isoforms; Receptor, Insulin; Receptors, Somatomedin; Signal Transduction; Somatomedins; Thyroid Neoplasms
PubMed: 31394114
DOI: 10.1016/j.bbamcr.2019.118522 -
Acta Physiologica (Oxford, England) Jun 2020
Topics: Animals; Cognition; Growth Hormone; Human Growth Hormone; Insulin-Like Growth Factor I; Learning; Rats
PubMed: 32271983
DOI: 10.1111/apha.13474 -
Oncogene Jun 2022The insulin-like growth factors (IGFs) and their regulatory proteins-IGF receptors and binding proteins-are strongly implicated in cancer progression and modulate cell... (Review)
Review
The insulin-like growth factors (IGFs) and their regulatory proteins-IGF receptors and binding proteins-are strongly implicated in cancer progression and modulate cell survival and proliferation, migration, angiogenesis and metastasis. By regulating the bioavailability of the type-1 IGF receptor (IGF1R) ligands, IGF-1 and IGF-2, the IGF binding proteins (IGFBP-1 to -6) play essential roles in cancer progression. IGFBPs also influence cell communications through pathways that are independent of IGF1R activation. Noncoding RNAs (ncRNAs), which encompass a variety of RNA types including microRNAs (miRNAs) and long-noncoding RNAs (lncRNAs), have roles in multiple oncogenic pathways, but their many points of intersection with IGF axis functions remain to be fully explored. This review examines the functional interactions of miRNAs and lncRNAs with IGFs and their binding proteins in cancer, and reveals how the IGF axis may mediate ncRNA actions that promote or suppress cancer. A better understanding of the links between ncRNA and IGF pathways may suggest new avenues for prognosis and therapeutic intervention in cancer. Further, by exploring examples of intersecting ncRNA-IGF pathways in non-cancer conditions, it is proposed that new opportunities for future discovery in cancer control may be generated.
Topics: Humans; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; MicroRNAs; Neoplasms; RNA, Long Noncoding; RNA, Untranslated; Receptors, Somatomedin
PubMed: 35597813
DOI: 10.1038/s41388-022-02353-3 -
Advances in Biological Regulation Dec 2019T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer, characterized by an uncontrolled expansion and accumulation of T-cell progenitors. During leukemic... (Review)
Review
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer, characterized by an uncontrolled expansion and accumulation of T-cell progenitors. During leukemic progression, immature T cells grow abnormally and occupy the bone marrow compartment, thereby interfering with the production of normal blood cells. Pediatric T-ALL is curable with intensive chemotherapy, but there are significant, long-term side effects and ~20% of patients suffer relapse for which there are limited treatment options. Adult T-ALL in contrast is largely incurable and refractory/relapsed disease is common despite multi-agent chemotherapy (5-year overall survival of ~40%), and thus new therapeutic targets are needed. We have reported previously on the role of insulin-like growth factor (IGF) signaling in T-ALL, and shown that it exerts potent phenotypes in both leukemia stem cell and bulk tumor cell populations. Modulators of IGF signaling may thus prove useful in improving outcomes in patients with T-ALL. In this review, we summarize the most recent findings relating to IGF signaling in T-ALL and outline therapeutic options using clinically relevant IGF signaling modulators.
Topics: Humans; Neoplasm Proteins; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Signal Transduction; Somatomedins
PubMed: 31543360
DOI: 10.1016/j.jbior.2019.100652