scholarly journals Reorganisation of chromatin during erythroid differentiation

2019 ◽  
Vol 23 (1) ◽  
pp. 95-99
Author(s):  
A. A. Khabarova ◽  
A. S. Ryzhkova ◽  
N. R. Battulin
Keyword(s):  
Chromatin Structure ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Erythroid Differentiation ◽  
Gene Activity ◽  
Nuclear Space ◽  
Specific Cell ◽  
Cell Type ◽  
Differentiation Potential

A totipotent zygote has unlimited potential for differentiation into all cell types found in an adult organism. During ontogenesis proliferating and maturing cells gradually lose their differentiation potential, limiting the spectrum of possible developmental transitions to a specific cell type. Following the initiation of the developmental program cells acquire specific morphological and functional properties. Deciphering the mechanisms that coordinate shifts in gene expression revealed a critical role of three-dimensional chromatin structure in the regulation of gene activity during lineage commitment. Several levels of DNA packaging have been recently identified using chromosome conformation capture based techniques such a Hi-C. It is now clear that chromatin regions with high transcriptional activity assemble into Mb-scale compartments in the nuclear space, distinct from transcriptionally silent regions. More locally chromatin is organized into topological domains, serving as functionally insulated units with cell type – specific regulatory loop interactions. However, molecular mechanisms establishing and maintaining such 3D organization are yet to be investigated. Recent focus on studying chromatin reorganization accompanying cell cycle progression and cellular differentiation partially explained some aspects of 3D genome folding. Throughout erythropoiesis cells undergo a dramatic reorganization of the chromatin landscape leading to global nuclear condensation and transcriptional silencing, followed by nuclear extrusion at the final stage of mammalian erythropoiesis. Drastic changes of genome architecture and function accompanying erythroid differentiation seem to be an informative model for studying the ways of how genome organization and dynamic gene activity are connected. Here we summarize current views on the role of global rearrangement of 3D chromatin structure in erythroid differentiation.

scholarly journals ASXL2 Is Required for Normal Hematopoiesis and Loss of asxl2 Leads to Myeloid Malignancies in Mice

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1509-1509
Author(s):  
Jianping Li ◽  
Fuhong He ◽  
Peng Zhang ◽  
Shi Chen ◽  
Hui Shi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Differentiation ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Myeloid Cell ◽  
Gene Set Enrichment Analysis ◽  
Differentiation Potential ◽  
Self Renewal ◽  
Myeloid Malignancies

Abstract Somatic mutations and chromosomal translocations of genes have emerged as major drivers in a range of hematopoietic malignancies. While ASXL1 is mutated in all forms of myeloid malignancies, ASXL2 is specifically mutated in t(8;21) AML patients. ASXL1 and ASXL2 mutations are mutually exclusive in t(8;21) AML. Despite the importance of ASXL2 mutations in clinical, it's role in leukemogenesis remain unknown. In the current study, we sought to dissect the role of ASXL2 in normal hematopoiesis and to identify the molecular mechanisms by which Asxl2 loss contributes to myeloid malignancies. In the current study, we utilized a mouse model of Asxl2 to characterize the hematopoietic features of in vivo. Asxl2-/- mice were characterized by pancytopenia and dysplastic features, including hyposegmented (bilobed) neutrophils with fine nuclear bridging (consistent with pseudo Pelger-Huët) and increased number of polychromatophilic red blood cells (RBCs), reminiscent of myelodysplastic syndrome (MDS). Flow cytometric analyses revealed that Asxl2-/- mice had an increased proportion of granulocytic/monocytic cells (Gr-1+/Mac1+) in the PB, BM and spleens compared to WT mice. The histologic analysis of the Asxl2+/- and Asxl2-/- spleen sections showed disrupted splenic architecture with an increased proportion of myeloid cells and massive accumulation of myeloperoxidase (MPO) positive cells in WT spleens. Asxl2-/- mice had an increased long-term (LH)-HSCs and granulocyte-macrophage progenitor (GMP) cells compared to WT mice.Consistently, the paired-daughter cell assays revealed that Asxl2-/- CD34-LSK BM cells had a higher proportion of cells with symmetric self-renewal capacity (SS, 62%) than WT cells (33%). In contrast, a significant reduction in the cells with symmetric differentiation potential was observed in Asxl2-/- HSCs (18%) compared to WT HSCs (40%), indicating a critical role of ASXL2 in the balance between the symmetric and asymmetric division of HSCs. Transplantation assays revealed that recipients transplanted with Asxl2-/- and Asxl2+/- bone marrow cells had shortened lifespan due to the development of MDS or AML, suggesting a cell-autonomous effect of Asxl2-loss in HSC/HPC functions. Furthermore, Asxl2-loss further increase the colony-forming potential and colony replating capacity of AML1-ETO expressing HSCs in vitro, suggesting a cooperative effect between AML1/ETO9a and Asxl2+/-to promote HSC self-renewal. RNA-seq analysis showed a unique signature of Asxl2-/- LK cells compared to WT LK cells. Gene set enrichment analysis revealed that altered expressed genes in Asxl2-/-LK cells were enriched in myeloid cell differentiation, hematopoiesis, apoptosis, and chromatin/nucleosome assembly signature. ChIP-seq analysis showed that differentially expressed genes were associated with dysregulated histone enhancer markers, including H3K27ac, H3K4me1, and H3K4me2. Further analysis demonstrated that the alteration of H3K27ac enrichment had a greater impact on gene expression, in comparison to H3K4me1/2. KEGG pathway analysis showed that genes with differential H3K27ac signals were enriched for hematopoietic cell lineage, cancer signaling pathway and myeloid leukemia development. IPA analysis further confirmed that genes with altered enrichment levels of were enriched in myeloid cell differentiation and apoptosis pathways. Altogether, these data suggest that ASXL2 regulates gene expression mainly through enhancer markers. Our results demonstrate that ASXL2 plays an important role in normal hematopoiesis, and Asxl2-loss in mice is sufficient to cause MDS-like disease and leukemia transformation. These results indicate that ASXL2 functions as a tumor suppressor in myelopoiesis. The Asxl2 knock-out mice present an ideal model for unveiling the mechanisms underlying the Asxl2-loss mediated multiple-step pathogenesis of myeloid malignancies and for testing novel therapeutic agents for myeloid malignant patients with ASXL2 alterations. Further studies to dissect the possible roles of ASXL2alterations in leukemogenesis and to identify therapeutic vulnerabilities they may create are ongoing. Disclosures No relevant conflicts of interest to declare.

The Role of the Endothelium in Premature Atherosclerosis: Molecular Mechanisms

2020 ◽  
Vol 27 (7) ◽  
pp. 1041-1051 ◽  
Author(s):  
Michael Spartalis ◽  
Eleftherios Spartalis ◽  
Antonios Athanasiou ◽  
Stavroula A. Paschou ◽  
Christos Kontogiannis ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Low Density Lipoprotein ◽  
Critical Role ◽  
Density Lipoprotein ◽  
Number Of Genes ◽  
Causes Of Mortality ◽  
Artery Disease ◽  
Genetic And Environmental Factors ◽  
Made In

Atherosclerotic disease is still one of the leading causes of mortality. Atherosclerosis is a complex progressive and systematic artery disease that involves the intima of the large and middle artery vessels. The inflammation has a key role in the pathophysiological process of the disease and the infiltration of the intima from monocytes, macrophages and T-lymphocytes combined with endothelial dysfunction and accumulated oxidized low-density lipoprotein (LDL) are the main findings of atherogenesis. The development of atherosclerosis involves multiple genetic and environmental factors. Although a large number of genes, genetic polymorphisms, and susceptible loci have been identified in chromosomal regions associated with atherosclerosis, it is the epigenetic process that regulates the chromosomal organization and genetic expression that plays a critical role in the pathogenesis of atherosclerosis. Despite the positive progress made in understanding the pathogenesis of atherosclerosis, the knowledge about the disease remains scarce.

LncRNA SNHG12 Improves Cerebral Ischemic-reperfusion Injury by Activating SIRT1/FOXO3a Pathway through I nhibition of Autophagy and Oxidative Stress

2020 ◽  
Vol 17 (4) ◽  
pp. 394-401
Author(s):  
Yuanhua Wu ◽  
Yuan Huang ◽  
Jing Cai ◽  
Donglan Zhang ◽  
Shixi Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Cell Activity ◽  
Ht22 Cells ◽  
Cerebral Ischemic ◽  
Cerebral Ischemic Reperfusion ◽  
And Oxidative Stress

Background: Ischemia/reperfusion (I/R) injury involves complex biological processes and molecular mechanisms such as autophagy. Oxidative stress plays a critical role in the pathogenesis of I/R injury. LncRNAs are the regulatory factor of cerebral I/R injury. Methods: This study constructs cerebral I/R model to investigate role of autophagy and oxidative stress in cerebral I/R injury and the underline regulatory mechanism of SIRT1/ FOXO3a pathway. In this study, lncRNA SNHG12 and FOXO3a expression was up-regulated and SIRT1 expression was down-regulated in HT22 cells of I/R model. Results: Overexpression of lncRNA SNHG12 significantly increased the cell viability and inhibited cerebral ischemicreperfusion injury induced by I/Rthrough inhibition of autophagy. In addition, the transfected p-SIRT1 significantly suppressed the release of LDH and SOD compared with cells co-transfected with SIRT1 and FOXO3a group and cells induced by I/R and transfected with p-SNHG12 group and overexpression of cells co-transfected with SIRT1 and FOXO3 further decreased the I/R induced release of ROS and MDA. Conclusion: In conclusion, lncRNA SNHG12 increased cell activity and inhibited oxidative stress through inhibition of SIRT1/FOXO3a signaling-mediated autophagy in HT22 cells of I/R model. This study might provide new potential therapeutic targets for further investigating the mechanisms in cerebral I/R injury and provide.

Metabolic Regulation and Related Molecular Mechanisms in Various Stem Cell Functions

2020 ◽  
Vol 15 (6) ◽  
pp. 531-546 ◽  
Author(s):  
Hwa-Yong Lee ◽  
In-Sun Hong
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Oxidative Phosphorylation ◽  
Metabolic Pathways ◽  
Critical Role ◽  
The Self ◽  
Specific Cell ◽  
Differentiation Potential ◽  
Self Renewal ◽  
Cell Functions

Recent studies on the mechanisms that link metabolic changes with stem cell fate have deepened our understanding of how specific metabolic pathways can regulate various stem cell functions during the development of an organism. Although it was originally thought to be merely a consequence of the specific cell state, metabolism is currently known to play a critical role in regulating the self-renewal capacity, differentiation potential, and quiescence of stem cells. Many studies in recent years have revealed that metabolic pathways regulate various stem cell behaviors (e.g., selfrenewal, migration, and differentiation) by modulating energy production through glycolysis or oxidative phosphorylation and by regulating the generation of metabolites, which can modulate multiple signaling pathways. Therefore, a more comprehensive understanding of stem cell metabolism could allow us to establish optimal culture conditions and differentiation methods that would increase stem cell expansion and function for cell-based therapies. However, little is known about how metabolic pathways regulate various stem cell functions. In this context, we review the current advances in metabolic research that have revealed functional roles for mitochondrial oxidative phosphorylation, anaerobic glycolysis, and oxidative stress during the self-renewal, differentiation and aging of various adult stem cell types. These approaches could provide novel strategies for the development of metabolic or pharmacological therapies to promote the regenerative potential of stem cells and subsequently promote their therapeutic utility.

scholarly journals Shisa6 mediates cell-type specific regulation of depression in the nucleus accumbens

2021 ◽  
Author(s):  
Hee-Dae Kim ◽  
Jing Wei ◽  
Tanessa Call ◽  
Nicole Teru Quintus ◽  
Alexander J. Summers ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Current Treatment ◽  
Specific Cell ◽  
Excitatory Synapses ◽  
Cell Type ◽  
Cell Type Specific ◽  
Specific Regulation ◽  
Circuit Function

AbstractDepression is the leading cause of disability and produces enormous health and economic burdens. Current treatment approaches for depression are largely ineffective and leave more than 50% of patients symptomatic, mainly because of non-selective and broad action of antidepressants. Thus, there is an urgent need to design and develop novel therapeutics to treat depression. Given the heterogeneity and complexity of the brain, identification of molecular mechanisms within specific cell-types responsible for producing depression-like behaviors will advance development of therapies. In the reward circuitry, the nucleus accumbens (NAc) is a key brain region of depression pathophysiology, possibly based on differential activity of D1- or D2- medium spiny neurons (MSNs). Here we report a circuit- and cell-type specific molecular target for depression, Shisa6, recently defined as an AMPAR component, which is increased only in D1-MSNs in the NAc of susceptible mice. Using the Ribotag approach, we dissected the transcriptional profile of D1- and D2-MSNs by RNA sequencing following a mouse model of depression, chronic social defeat stress (CSDS). Bioinformatic analyses identified cell-type specific genes that may contribute to the pathogenesis of depression, including Shisa6. We found selective optogenetic activation of the ventral tegmental area (VTA) to NAc circuit increases Shisa6 expression in D1-MSNs. Shisa6 is specifically located in excitatory synapses of D1-MSNs and increases excitability of neurons, which promotes anxiety- and depression-like behaviors in mice. Cell-type and circuit-specific action of Shisa6, which directly modulates excitatory synapses that convey aversive information, identifies the protein as a potential rapid-antidepressant target for aberrant circuit function in depression.

scholarly journals The laterodorsal tegmentum-ventral tegmental area circuit controls depression-like behaviors by activating ErbB4 in DA neurons

2021 ◽  
Author(s):  
Hongsheng Wang ◽  
Wanpeng Cui ◽  
Wenbing Chen ◽  
Fang Liu ◽  
Zhaoqi Dong ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Coping With Stress ◽  
Chemical Genetic ◽  
Chronic Social Defeat Stress ◽  
Ventral Tegmental ◽  
Laterodorsal Tegmentum ◽  
Specific Deletion

AbstractDopamine (DA) neurons in the ventral tegmental area (VTA) are critical to coping with stress. However, molecular mechanisms regulating their activity and stress-induced depression were not well understood. We found that the receptor tyrosine kinase ErbB4 in VTA was activated in stress-susceptible mice. Deleting ErbB4 in VTA or in DA neurons, or chemical genetic inhibition of ErbB4 kinase activity in VTA suppressed the development of chronic social defeat stress (CSDS)-induced depression-like behaviors. ErbB4 activation required the expression of NRG1 in the laterodorsal tegmentum (LDTg); LDTg-specific deletion of NRG1 inhibited depression-like behaviors. NRG1 and ErbB4 suppressed potassium currents of VTA DA neurons and increased their firing activity. Finally, we showed that acute inhibition of ErbB4 after stress attenuated DA neuron hyperactivity and expression of depression-like behaviors. Together, these observations demonstrate a critical role of NRG1-ErbB4 signaling in regulating depression-like behaviors and identify an unexpected mechanism by which the LDTg-VTA circuit regulates the activity of DA neurons.

scholarly journals Suppression of eNOS-derived superoxide by caveolin-1: a biopterin-dependent mechanism

2011 ◽  
Vol 301 (3) ◽  
pp. H903-H911 ◽  
Author(s):  
Kanchana Karuppiah ◽  
Lawrence J. Druhan ◽  
Chun-an Chen ◽  
Travis Smith ◽  
Jay L. Zweier ◽  
...  
Keyword(s):  
Gene Silencing ◽  
Oxidase Activity ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Caveolin 1 ◽  
Calcium Calmodulin Dependent ◽  
Enos Uncoupling ◽  
Nadph Oxidation ◽  
Interfering Rna

In the vasculature, nitric oxide (NO) is generated by endothelial NO synthase (eNOS) in a calcium/calmodulin-dependent reaction. In the absence of the requisite eNOS cofactor tetrahydrobiopterin (BH4), NADPH oxidation is uncoupled from NO generation, leading to the production of superoxide. Although this phenomenon is apparent with purified enzyme, cellular studies suggest that formation of the BH4 oxidation product, dihydrobiopterin, is the molecular trigger for eNOS uncoupling rather than BH4 depletion alone. In the current study, we investigated the effects of both BH4 depletion and oxidation on eNOS-derived superoxide production in endothelial cells in an attempt to elucidate the molecular mechanisms regulating eNOS oxidase activity. Results demonstrated that pharmacological depletion of endothelial BH4 does not result in eNOS oxidase activity, whereas BH4 oxidation gave rise to significant eNOS-oxidase activity. These findings suggest that the endothelium possesses regulatory mechanisms, which prevent eNOS oxidase activity from pterin-free eNOS. Using a combination of gene silencing and pharmacological approaches, we demonstrate that eNOS-caveolin-1 association is increased under conditions of reduced pterin bioavailability and that this sequestration serves to suppress eNOS uncoupling. Using small interfering RNA approaches, we demonstrate that caveolin-1 gene silencing increases eNOS oxidase activity to 85% of that observed under conditions of BH4 oxidation. Moreover, when caveolin-1 silencing was combined with a pharmacological inhibitor of AKT, BH4 depletion increased eNOS-derived superoxide to 165% of that observed with BH4 oxidation. This study identifies a critical role of caveolin-1 in the regulation of eNOS uncoupling and provides new insight into the mechanisms through which disease-associated changes in caveolin-1 expression may contribute to endothelial dysfunction.

scholarly journals Single-Cell Transcriptomic Analysis Revealed a Critical Role of SPP1/CD44-Mediated Crosstalk Between Macrophages and Cancer Cells in Glioma

2021 ◽  
Vol 9 ◽  
Author(s):  
Cong He ◽  
Luoyan Sheng ◽  
Deshen Pan ◽  
Shuai Jiang ◽  
Li Ding ◽  
...  
Keyword(s):  
Single Cell ◽  
Tumor Heterogeneity ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Cell Communication ◽  
High Grade Glioma ◽  
Sequencing Analysis ◽  
High Grade ◽  
Cellular Components

High-grade glioma is one of the most lethal human cancers characterized by extensive tumor heterogeneity. In order to identify cellular and molecular mechanisms that drive tumor heterogeneity of this lethal disease, we performed single-cell RNA sequencing analysis of one high-grade glioma. Accordingly, we analyzed the individual cellular components in the ecosystem of this tumor. We found that tumor-associated macrophages are predominant in the immune microenvironment. Furthermore, we identified five distinct subpopulations of tumor cells, including one cycling, two OPC/NPC-like and two MES-like cell subpopulations. Moreover, we revealed the evolutionary transition from the cycling to OPC/NPC-like and MES-like cells by trajectory analysis. Importantly, we found that SPP1/CD44 interaction plays a critical role in macrophage-mediated activation of MES-like cells by exploring the cell-cell communication among all cellular components in the tumor ecosystem. Finally, we showed that high expression levels of both SPP1 and CD44 correlate with an increased infiltration of macrophages and poor prognosis of glioma patients. Taken together, this study provided a single-cell atlas of one high-grade glioma and revealed a critical role of macrophage-mediated SPP1/CD44 signaling in glioma progression, indicating that the SPP1/CD44 axis is a potential target for glioma treatment.

scholarly journals Maternal Hepcidin Suppression Is Essential for Healthy Pregnancy

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 43-44
Author(s):  
Veena Sangkhae ◽  
Tomas Ganz ◽  
Elizabeta Nemeth
Keyword(s):  
Iron Deficiency ◽  
Molecular Mechanisms ◽  
Hematological Parameters ◽  
Critical Role ◽  
Physiological Mechanism ◽  
Deficiency Anemia ◽  
Private Company ◽  
Iron Stores ◽  
Primary Mouse

Iron is essential for maternal and fetal health during pregnancy, and iron requirements increase substantially in the second half of gestation1. However, the molecular mechanisms ensuring increased iron availability during pregnancy are not well understood. Hepcidin is the key iron-regulatory hormone and functions by occluding and degrading the iron exporter ferroportin (FPN) to inhibit dietary iron absorption and mobilization of iron from stores. In healthy human and rodent pregnancies, maternal hepcidin decreases starting in the second trimester and is nearly undetectable by late pregnancy2,3 (Figure A). We explored the role of maternal and embryo hepcidin in regulating embryo iron endowment using mouse models. By generating combinations of dams and embryos lacking hepcidin or not, we showed that in normal mouse pregnancy, only maternal but not embryo or placental hepcidin determines embryo iron endowment4. Maternal hepcidin was inversely related to embryo iron stores, and embryos from hepcidin-deficient dams had significantly higher hepatic iron stores regardless of their own hepcidin genotype. When maternal hepcidin was elevated during the second half of pregnancy in mice by administering a hepcidin mimetic, this led to dose-dependent embryo iron deficiency, anemia, and in severe cases, embryo death4. Embryos were particularly sensitive to maternal iron restriction as they developed iron deficiency in the liver and the brain even when maternal hematological parameters were unaffected. These data highlight the critical role of maternal hepcidin suppression for heathy pregnancy. Yet, the physiological mechanism of maternal hepcidin suppression remains unknown. We showed in mice that maternal hepcidin decreases prior to a significant decrease in liver iron and without any changes in serum iron, suggesting that maternal hepcidin suppression is not driven solely by iron deficiency. Using an in vitro model, we determined that the placenta secretes a hepcidin-suppressing factor. Exposure of primary mouse hepatocytes to supernatants from cultured human placenta cells, but not control media, suppressed hepcidin mRNA more than 10-fold (Figure B) and for up to 48hrs. The suppressive factor in the supernatant was >100kDa in size and not associated with exosomes. Studies to identify the placenta-derived hepcidin suppressor are ongoing. In summary, suppression of maternal hepcidin is essential to ensure adequate iron supply for transfer to the fetus and for the increase in maternal red blood cell mass2, and a placenta-derived hepcidin suppressor likely plays an important role in this adaptation. 1Fisher AL and Nemeth E, Am J Clin Nutr, 2017 2Sangkhae V et al, JCI, 2020 3van Santen S et al, Clin Chem Lab Med, 2013 4Sangkhae V et al, Blood, 2020 Figure 1 Disclosures Ganz: Global Blood Therapeutics: Consultancy; Ionis Pharmaceuticals: Consultancy; American Regent: Consultancy; Rockwell: Consultancy; Vifor: Consultancy; Astellas: Consultancy; Akebia: Consultancy; Gossamer Bio: Consultancy; Silarus Therapeutics: Current equity holder in private company; Sierra Oncology: Consultancy; Ambys: Consultancy; Disc Medicine: Consultancy; Intrinsic LifeSciences: Current equity holder in private company. Nemeth:Intrinsic LifeSciences: Current equity holder in private company; Silarus Therapeutics: Current equity holder in private company; Ionis Pharmaceuticals: Consultancy; Protagonist: Consultancy; Vifor: Consultancy.

scholarly journals Emerging roles of the Hedgehog signalling pathway in inflammatory bowel disease

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Zhuo Xie ◽  
Mudan Zhang ◽  
Gaoshi Zhou ◽  
Lihui Lin ◽  
Jing Han ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Molecular Mechanisms ◽  
Treatment Options ◽  
Critical Role ◽  
Signalling Pathway ◽  
Hedgehog Signalling Pathway ◽  
Inflammatory Bowel ◽  
Effective Drugs

AbstractThe Hedgehog (Hh) signalling pathway plays a critical role in the growth and patterning during embryonic development and maintenance of adult tissue homeostasis. Emerging data indicate that Hh signalling is implicated in the pathogenesis of inflammatory bowel disease (IBD). Current therapeutic treatments for IBD require optimisation, and novel effective drugs are warranted. Targeting the Hh signalling pathway may pave the way for successful IBD treatment. In this review, we introduce the molecular mechanisms underlying the Hh signalling pathway and its role in maintaining intestinal homeostasis. Then, we present interactions between the Hh signalling and other pathways involved in IBD and colitis-associated colorectal cancer (CAC), such as the Wnt and nuclear factor-kappa B (NF-κB) pathways. Furthermore, we summarise the latest research on Hh signalling associated with the occurrence and progression of IBD and CAC. Finally, we discuss the future directions for research on the role of Hh signalling in IBD pathogenesis and provide viewpoints on novel treatment options for IBD by targeting Hh signalling. An in-depth understanding of the complex role of Hh signalling in IBD pathogenesis will contribute to the development of new effective therapies for IBD patients.

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