scholarly journals The Canonical Wnt Pathway as a Key Regulator in Liver Development, Differentiation and Homeostatic Renewal

Genes ◽  
2020 ◽  
Vol 11 (10) ◽  
pp. 1163
Author(s):  
Sebastian L. Wild ◽  
Aya Elghajiji ◽  
Carmen Grimaldos Rodriguez ◽  
Stephen D. Weston ◽  
Zoë D. Burke ◽  
...  
Keyword(s):  
Critical Role ◽  
Hypoxia Inducible Factor ◽  
Signalling Pathway ◽  
Fate Specification ◽  
Cellular Processes ◽  
Recent Developments ◽  
Body Patterning ◽  
Important Regulator ◽  
Canonical Wnt

The canonical Wnt (Wnt/β-catenin) signalling pathway is highly conserved and plays a critical role in regulating cellular processes both during development and in adult tissue homeostasis. The Wnt/β-catenin signalling pathway is vital for correct body patterning and is involved in fate specification of the gut tube, the primitive precursor of liver. In adults, the Wnt/β-catenin pathway is increasingly recognised as an important regulator of metabolic zonation, homeostatic renewal and regeneration in response to injury throughout the liver. Herein, we review recent developments relating to the key role of the pathway in the patterning and fate specification of the liver, in the directed differentiation of pluripotent stem cells into hepatocytes and in governing proliferation and zonation in the adult liver. We pay particular attention to recent contributions to the controversy surrounding homeostatic renewal and proliferation in response to injury. Furthermore, we discuss how crosstalk between the Wnt/β-catenin and Hedgehog (Hh) and hypoxia inducible factor (HIF) pathways works to maintain liver homeostasis. Advancing our understanding of this pathway will benefit our ability to model disease, screen drugs and generate tissue and organ replacements for regenerative medicine.

scholarly journals The State of the Art and Prospects for Osteoimmunomodulatory Biomaterials

Materials ◽  
2021 ◽  
Vol 14 (6) ◽  
pp. 1357
Author(s):  
Andreea-Mariana Negrescu ◽  
Anisoara Cimpean
Keyword(s):  
Foreign Bodies ◽  
Structural Characteristics ◽  
Critical Role ◽  
Fibrous Tissue ◽  
Bioactive Molecules ◽  
New Bone Formation ◽  
Recent Developments

The critical role of the immune system in host defense against foreign bodies and pathogens has been long recognized. With the introduction of a new field of research called osteoimmunology, the crosstalk between the immune and bone-forming cells has been studied more thoroughly, leading to the conclusion that the two systems are intimately connected through various cytokines, signaling molecules, transcription factors and receptors. The host immune reaction triggered by biomaterial implantation determines the in vivo fate of the implant, either in new bone formation or in fibrous tissue encapsulation. The traditional biomaterial design consisted in fabricating inert biomaterials capable of stimulating osteogenesis; however, inconsistencies between the in vitro and in vivo results were reported. This led to a shift in the development of biomaterials towards implants with osteoimmunomodulatory properties. By endowing the orthopedic biomaterials with favorable osteoimmunomodulatory properties, a desired immune response can be triggered in order to obtain a proper bone regeneration process. In this context, various approaches, such as the modification of chemical/structural characteristics or the incorporation of bioactive molecules, have been employed in order to modulate the crosstalk with the immune cells. The current review provides an overview of recent developments in such applied strategies.

scholarly journals Targeting microRNAs to Regulate the Integrity of the Blood–Brain Barrier

2021 ◽  
Vol 9 ◽  
Author(s):  
Juntao Wang ◽  
Fang Xu ◽  
Xiaoming Zhu ◽  
Xianghua Li ◽  
Yankun Li ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Neurovascular Unit ◽  
Cerebrovascular Diseases ◽  
Brain Parenchyma ◽  
Brain Barrier ◽  
Brain Diseases ◽  
Blood Brain ◽  
Recent Developments ◽  
Important Regulator

The blood–brain barrier (BBB) is a highly specialized neurovascular unit that protects the brain from potentially harmful substances. In addition, the BBB also engages in the exchange of essential nutrients between the vasculature and brain parenchyma, which is critical for brain homeostasis. Brain diseases, including neurological disorders and cerebrovascular diseases, are often associated with disrupted BBB integrity, evidenced by increased permeability. Therefore, defining the mechanisms underlying the regulation of BBB integrity is crucial for the development of novel therapeutics targeting brain diseases. MicroRNAs (miRNA), a type of small non-coding RNAs, are emerging as an important regulator of BBB integrity. Here we review recent developments related to the role of miRNAs in regulating BBB integrity.

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.

scholarly journals Immunoepigenetics Combination Therapies: An Overview of the Role of HDACs in Cancer Immunotherapy

2019 ◽  
Vol 20 (9) ◽  
pp. 2241 ◽  
Author(s):  
Debarati Banik ◽  
Sara Moufarrij ◽  
Alejandro Villagra
Keyword(s):  
Histone Deacetylase Inhibitors ◽  
Critical Role ◽  
Preclinical Studies ◽  
Clinical Use ◽  
Combination Therapies ◽  
Drug Candidates ◽  
Cellular Processes ◽  
Fda Approval

Long-standing efforts to identify the multifaceted roles of histone deacetylase inhibitors (HDACis) have positioned these agents as promising drug candidates in combatting cancer, autoimmune, neurodegenerative, and infectious diseases. The same has also encouraged the evaluation of multiple HDACi candidates in preclinical studies in cancer and other diseases as well as the FDA-approval towards clinical use for specific agents. In this review, we have discussed how the efficacy of immunotherapy can be leveraged by combining it with HDACis. We have also included a brief overview of the classification of HDACis as well as their various roles in physiological and pathophysiological scenarios to target key cellular processes promoting the initiation, establishment, and progression of cancer. Given the critical role of the tumor microenvironment (TME) towards the outcome of anticancer therapies, we have also discussed the effect of HDACis on different components of the TME. We then have gradually progressed into examples of specific pan-HDACis, class I HDACi, and selective HDACis that either have been incorporated into clinical trials or show promising preclinical effects for future consideration. Finally, we have included examples of ongoing trials for each of the above categories of HDACis as standalone agents or in combination with immunotherapeutic approaches.

scholarly journals c-Cbl: An Important Regulator and a Target in Angiogenesis and Tumorigenesis

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 498 ◽  
Author(s):  
Chimera L. Lyle ◽  
Mostafa Belghasem ◽  
Vipul C. Chitalia
Keyword(s):  
Therapeutic Potential ◽  
Critical Role ◽  
Modular Function ◽  
Signaling Cascades ◽  
Solid Organ ◽  
Multifunctional Protein ◽  
Ubiquitin E3 Ligase ◽  
Important Regulator ◽  
B Lineage

Casitas B lineage lymphoma (c-Cbl) is a multifunctional protein with a ubiquitin E3 ligase activity capable of degrading diverse sets of proteins. Although previous work had focused mainly on c-Cbl mutations in humans with hematological malignancies, recent emerging evidence suggests a critical role of c-Cbl in angiogenesis and human solid organ tumors. The combination of its unique structure, modular function, and ability to channelize cues from a rich network of signaling cascades, empowers c-Cbl to assume a central role in these disease models. This review consolidates the structural and functional insights based on recent studies that highlight c-Cbl as a target with tantalizing therapeutic potential in various models of angiogenesis and tumorigenesis.

scholarly journals 55th Bowditch Lecture: Effects of chronic hypoxia on the pulmonary circulation: Role of HIF-1

2012 ◽  
Vol 113 (9) ◽  
pp. 1343-1352 ◽  
Author(s):  
Larissa A. Shimoda
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Circulation ◽  
Vascular Remodeling ◽  
Chronic Hypoxia ◽  
Critical Role ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1 ◽  
Pulmonary Arterial ◽  
Expression And Activity

When exposed to chronic hypoxia (CH), the pulmonary circulation responds with enhanced contraction and vascular remodeling, resulting in elevated pulmonary arterial pressures. Our work has identified CH-induced alterations in the expression and activity of several ion channels and transporters in pulmonary vascular smooth muscle that contribute to the development of hypoxic pulmonary hypertension and uncovered a critical role for the transcription factor hypoxia-inducible factor-1 (HIF-1) in mediating these responses. Current work is focused on the regulation of HIF in the chronically hypoxic lung and evaluation of the potential for pharmacological inhibitors of HIF to prevent, reverse, or slow the progression of pulmonary hypertension.

Crosstalk between TGF-β1 signalling pathway and microRNAs in renal cancer

2020 ◽  
Vol 7 ◽  
pp. 1-14
Author(s):  
Joanna Bogusławska
Keyword(s):  
Renal Cancer ◽  
Potential Role ◽  
Signalling Pathway ◽  
Small Noncoding Rnas ◽  
Cellular Processes ◽  
Genes Expression ◽  
Mutual Regulation ◽  
Important Regulator ◽  
Oncogenic Function ◽  
Tgf Β1

Alterations in TGF-β1 signalling in renal cancer are accompanied by disturbed expression of microRNAs (miRNAs). TGF-β1 is an important regulator of key cellular processes and contributes to the development of many diseases, including cancer. At early cancer stages, TGF-β1 inhibits proliferation and tumour growth, while as the disease progresses, TGF-β1 stimulates metastasis. This dual TGF-β1 effect in cancers is called the “TGF-β1 paradox”. miRNAs – small, noncoding RNAs which regulate genes expression may contribute to the switching of TGF-β1 from suppressor to oncogenic function. The article presents the latest information regarding mutual regulation between miRNAs and the TGF-β1 signalling pathway as well as its potential role in the treatment of kidney cancer.

The critical role of mast cell-derived hypoxia-inducible factor-1α in human and mice melanoma growth

2012 ◽  
Vol 132 (11) ◽  
pp. 2492-2501 ◽  
Author(s):  
Hyun-Ja Jeong ◽  
Hyun-A Oh ◽  
Sun-Young Nam ◽  
Na-Ra Han ◽  
Young-Sick Kim ◽  
...  
Keyword(s):  
Mast Cell ◽  
Critical Role ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1Α ◽  
Melanoma Growth

scholarly journals Targeting mediators of Wnt signalling pathways by GnRH in gonadotropes

2010 ◽  
Vol 44 (4) ◽  
pp. 195-201 ◽  
Author(s):  
Samantha Gardner ◽  
Emmanouil Stavrou ◽  
Patricia E Rischitor ◽  
Elena Faccenda ◽  
Adam J Pawson
Keyword(s):  
Signal Transduction ◽  
Gnrh Receptor ◽  
Wnt Signalling ◽  
Signalling Pathway ◽  
Signalling Pathways ◽  
Signal Transduction Pathways ◽  
Cellular Processes ◽  
Key Players ◽  
Canonical Wnt ◽  
Recent Demonstration

The binding of GnRH to its receptor on pituitary gonadotropes leads to the targeting of a diverse array of signalling mediators. These mediators drive multiple signal transduction pathways, which in turn regulate a variety of cellular processes, including the biosynthesis and secretion of the gonadotropins LH and FSH. Advances in our understanding of the mechanisms and signalling pathways that are recruited to regulate gonadotrope function are continually being made. This review will focus on the recent demonstration that key mediators of the canonical Wnt signalling pathway are targeted by GnRH in gonadotropes, and that these may play essential roles in regulating the expression of many of the key players in gonadotrope biology, including the GnRH receptor and the gonadotropins.

scholarly journals Positive-strand RNA viruses stimulate host phosphatidylcholine synthesis at viral replication sites

2016 ◽  
Vol 113 (8) ◽  
pp. E1064-E1073 ◽  
Author(s):  
Jiantao Zhang ◽  
Zhenlu Zhang ◽  
Vineela Chukkapalli ◽  
Jules A. Nchoutmboube ◽  
Jianhui Li ◽  
...  
Keyword(s):  
Viral Replication ◽  
Rna Viruses ◽  
Critical Role ◽  
Brome Mosaic Virus ◽  
Alternate Host ◽  
Positive Strand ◽  
Cellular Processes ◽  
Replication Sites ◽  
Positive Strand Rna

All positive-strand RNA viruses reorganize host intracellular membranes to assemble their viral replication complexes (VRCs); however, how these viruses modulate host lipid metabolism to accommodate such membrane proliferation and rearrangements is not well defined. We show that a significantly increased phosphatidylcholine (PC) content is associated with brome mosaic virus (BMV) replication in both natural host barley and alternate host yeast based on a lipidomic analysis. Enhanced PC levels are primarily associated with the perinuclear ER membrane, where BMV replication takes place. More specifically, BMV replication protein 1a interacts with and recruits Cho2p (choline requiring 2), a host enzyme involved in PC synthesis, to the site of viral replication. These results suggest that PC synthesized at the site of VRC assembly, not the transport of existing PC, is responsible for the enhanced accumulation. Blocking PC synthesis by deleting theCHO2gene resulted in VRCs with wider diameters than those in wild-type cells; however, BMV replication was significantly inhibited, highlighting the critical role of PC in VRC formation and viral replication. We further show that enhanced PC levels also accumulate at the replication sites of hepatitis C virus and poliovirus, revealing a conserved feature among a group of positive-strand RNA viruses. Our work also highlights a potential broad-spectrum antiviral strategy that would disrupt PC synthesis at the sites of viral replication but would not alter cellular processes.

Sign in / Sign up

Export Citation Format

Share Document