scholarly journals Shedding light on the role of keratinocyte-derived extracellular vesicles on skin-homing cells

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Golara Nasiri ◽  
Negar Azarpira ◽  
Aliakbar Alizadeh ◽  
Sanaz Goshtasbi ◽  
Lobat Tayebi
Keyword(s):  
Extracellular Vesicles ◽  
Lipid Membranes ◽  
Inflammatory Cells ◽  
Therapeutic Approaches ◽  
Cellular Functions ◽  
Skin Cells ◽  
Physiological Properties ◽  
Cutaneous Immunity ◽  
Skin Homing

Abstract Extracellular vesicles (EVs) are secretory lipid membranes with the ability to regulate cellular functions by exchanging biological components between different cells. Resident skin cells such as keratinocytes, fibroblasts, melanocytes, and inflammatory cells can secrete different types of EVs depending on their biological state. These vesicles can influence the physiological properties and pathological processes of skin, such as pigmentation, cutaneous immunity, and wound healing. Since keratinocytes constitute the majority of skin cells, secreted EVs from these cells may alter the pathophysiological behavior of other skin cells. This paper reviews the contents of keratinocyte-derived EVs and their impact on fibroblasts, melanocytes, and immune cells to provide an insight for better understanding of the pathophysiological mechanisms of skin disorders and their use in related therapeutic approaches.

scholarly journals Targeting Hedgehog Signalling through the Ubiquitylation Process: The Multiple Roles of the HECT-E3 Ligase Itch

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 98 ◽  
Author(s):  
Paola Infante ◽  
Ludovica Lospinoso Severini ◽  
Flavia Bernardi ◽  
Francesca Bufalieri ◽  
Lucia Di Marcotullio
Keyword(s):  
E3 Ligase ◽  
Multiple Roles ◽  
Post Translational Modification ◽  
Therapeutic Approaches ◽  
Cellular Functions ◽  
Hedgehog Signalling ◽  
Promising Target ◽  
Important Pathway ◽  
Multiple Levels

Hedgehog signalling (Hh) is a developmental conserved pathway strongly involved in cancers when deregulated. This important pathway is orchestrated by numerous regulators, transduces through distinct routes and is finely tuned at multiple levels. In this regard, ubiquitylation processes stand as essential for controlling Hh pathway output. Although this post-translational modification governs proteins turnover, it is also implicated in non-proteolytic events, thereby regulating the most important cellular functions. The HECT E3 ligase Itch, well known to control immune response, is emerging to have a pivotal role in tumorigenesis. By illustrating Itch specificities on Hh signalling key components, here we review the role of this HECT E3 ubiquitin ligase in suppressing Hh-dependent tumours and explore its potential as promising target for innovative therapeutic approaches.

scholarly journals The Role of Extracellular Vesicles in Cutaneous Remodeling and Hair Follicle Dynamics

2019 ◽  
Vol 20 (11) ◽  
pp. 2758 ◽  
Author(s):  
Elisa Carrasco ◽  
Gonzalo Soto-Heredero ◽  
María Mittelbrunn
Keyword(s):  
Hair Follicle ◽  
Extracellular Vesicles ◽  
Cell Function ◽  
Hair Follicles ◽  
The Body ◽  
Epithelial Stem Cells ◽  
Therapeutic Approaches ◽  
Waste Products ◽  
Efficient Treatment

Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are cell-derived membranous structures that were originally catalogued as a way of releasing cellular waste products. Since the discovery of their function in intercellular communication as carriers of proteins, lipids, and DNA and RNA molecules, numerous therapeutic approaches have focused on the use of EVs, in part because of their minimized risk compared to cell-based therapies. The skin is the organ with the largest surface in the body. Besides the importance of its body barrier function, much attention has been paid to the skin in regenerative medicine because of its cosmetic aspect, which is closely related to disorders affecting pigmentation and the presence or absence of hair follicles. The use of exosomes in therapeutic approaches for cutaneous wound healing has been reported and is briefly reviewed here. However, less attention has been paid to emerging interest in the potential capacity of EVs as modulators of hair follicle dynamics. Hair follicles are skin appendices that mainly comprise an epidermal and a mesenchymal component, with the former including a major reservoir of epithelial stem cells but also melanocytes and other cell types. Hair follicles continuously cycle, undergoing consecutive phases of resting, growing, and regression. Many biomolecules carried by EVs have been involved in the control of the hair follicle cycle and stem cell function. Thus, investigating the role of either naturally produced or therapeutically delivered EVs as signaling vehicles potentially involved in skin homeostasis and hair cycling may be an important step in the attempt to design future strategies towards the efficient treatment of several skin disorders.

scholarly journals Enhanced circulating levels of CD3 cells-derived extracellular vesicles in different forms of pulmonary hypertension

2019 ◽  
Vol 9 (3) ◽  
pp. 204589401986435 ◽  
Author(s):  
Djuro Kosanovic ◽  
Ujjwal Deo ◽  
Henning Gall ◽  
Balachandar Selvakumar ◽  
Susanne Herold ◽  
...  
Keyword(s):  
T Cells ◽  
Endothelial Cells ◽  
Pulmonary Hypertension ◽  
Extracellular Vesicles ◽  
Inflammatory Cells ◽  
Circulating Endothelial Cells ◽  
Profound Knowledge ◽  
Life Threatening ◽  
Circulating Levels

It has been shown previously that increased circulating endothelial cells-derived extracellular vesicles represent an important pathological attribute of pulmonary hypertension. Although it is a well-known fact that inflammatory cells may also release extracellular vesicles, and pulmonary hypertension is a disease associated with abnormal inflammation, there is no profound knowledge with regard to the role of inflammatory cells-derived extracellular vesicles. Therefore, our study demonstrated that circulating levels of extracellular vesicles derived from T-cells are enhanced in various pulmonary hypertension forms and that endothelial cells-derived extracellular vesicles may have distinctive profiles in different clinical subgroups of pulmonary hypertension, which still remains as a poorly treatable and life-threatening disorder.

scholarly journals Nitrosative Stress in Retinal Pathologies: Review

Antioxidants ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 543 ◽  
Author(s):  
Antolin Cantó ◽  
Teresa Olivar ◽  
Francisco Javier Romero ◽  
María Miranda
Keyword(s):  
Lipid Membranes ◽  
Nitrosative Stress ◽  
Age Related Macular Degeneration ◽  
Retinal Blood Flow ◽  
Vascular Endothelial ◽  
Nitrogen Species ◽  
Cellular Functions ◽  
Age Related ◽  
Retinal Pathologies

Nitric oxide (NO) is a gas molecule with diverse physiological and cellular functions. In the eye, NO is used to maintain normal visual function as it is involved in photoreceptor light transduction. In addition, NO acts as a rapid vascular endothelial relaxant, is involved in the control of retinal blood flow under basal conditions and mediates the vasodilator responses of different substances such as acetylcholine, bradykinin, histamine, substance P or insulin. However, the retina is rich in polyunsaturated lipid membranes and is sensitive to the action of reactive oxygen and nitrogen species. Products generated from NO (i.e., dinitrogen trioxide (N2O3) and peroxynitrite) have great oxidative damaging effects. Oxygen and nitrogen species can react with biomolecules (lipids, proteins and DNA), potentially leading to cell death, and this is particularly important in the retina. This review focuses on the role of NO in several ocular diseases, including diabetic retinopathy, retinitis pigmentosa, glaucoma or age-related macular degeneration (AMD).

scholarly journals A REVIEW ON ROLE OF TRPV CATION CHANNELS

2021 ◽  
Vol 10 (2) ◽  
pp. 32-51
Author(s):  
Deep Sharma ◽  
Rekha Rana ◽  
Kiran Thakur
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Cation Channels ◽  
Cellular Functions ◽  
Physiological Properties ◽  
Transient Receptor

The mammalian branch of the Transient Receptor Potential (TRP) superfamily of cation channels consists of 28 members. They can be subdivided in six main subfamilies: the TRPC (‘Canonical’), TRPV (‘Vanilloid’), TRPM (‘Melastatin’), TRPP (‘Polycystin’), TRPML (‘Mucolipin’) and the TRPA (‘Ankyrin’) group. The TRPV subfamily comprises channels that are critically involved in nociception and thermo-sensing (TRPV1, TRPV2, TRPV3, TRPV4) as well as highly Ca2+ selective channels involved in Ca2+ absorption/ reabsorption in mammals (TRPV5, TRPV6). In this review we summarize fundamental physiological properties of all TRPV members in the light of various cellular functions of these channels and their significance in the various diseases.

scholarly journals The Role of Extracellular Vesicles in the Hallmarks of Cancer and Drug Resistance

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1141 ◽  
Author(s):  
Cristina P. R. Xavier ◽  
Hugo R. Caires ◽  
Mélanie A. G. Barbosa ◽  
Rui Bergantim ◽  
José E. Guimarães ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Extracellular Vesicles ◽  
Genetic Material ◽  
Human Tumor ◽  
Current Evidence ◽  
Drug Resistant ◽  
Intercellular Signaling ◽  
Therapeutic Approaches ◽  
Intercellular Exchange

Extracellular vesicles (EVs) mediate intercellular signaling and communication, allowing the intercellular exchange of proteins, lipids, and genetic material. Their recognized role in the maintenance of the physiological balance and homeostasis seems to be severely disturbed throughout the carcinogenesis process. Indeed, the modus operandi of cancer implies the highjack of the EV signaling network to support tumor progression in many (if not all) human tumor malignancies. We have reviewed the current evidence for the role of EVs in affecting cancer hallmark traits by: (i) promoting cell proliferation and escape from apoptosis, (ii) sustaining angiogenesis, (iii) contributing to cancer cell invasion and metastasis, (iv) reprogramming energy metabolism, (v) transferring mutations, and (vi) modulating the tumor microenvironment (TME) by evading immune response and promoting inflammation. Special emphasis was given to the role of EVs in the transfer of drug resistant traits and to the EV cargo responsible for this transfer, both between cancer cells or between the microenvironment and tumor cells. Finally, we reviewed evidence for the increased release of EVs by drug resistant cells. A timely and comprehensive understanding of how tumor EVs facilitate tumor initiation, progression, metastasis and drug resistance is instrumental for the development of innovative EV-based therapeutic approaches for cancer.

scholarly journals Extracellular Vesicles in Viral Pathogenesis: A Case of Dr. Jekyll and Mr. Hyde

Life ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 45
Author(s):  
Lada Purvinsh ◽  
Andrey Gorshkov ◽  
Aleksandra Brodskaia ◽  
Andrey Vasin
Keyword(s):  
Extracellular Vesicles ◽  
Protective Factor ◽  
Fundamental Property ◽  
Molecular Composition ◽  
Biologically Active ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Physiological Processes ◽  
Infected Cells

Secretion of extracellular vesicles (EVs) is a fundamental property of living cells. EVs are known to transfer biological signals between cells and thus regulate the functional state of recipient cells. Such vesicles mediate the intercellular transport of many biologically active molecules (proteins, nucleic acids, specific lipids) and participate in regulation of key physiological processes. In addition, EVs are involved in the pathogenesis of multiple diseases: infectious, neurodegenerative, and oncological. The current EV classification into microvesicles, apoptotic bodies, and exosomes is based on their size, pathways of cellular biogenesis, and molecular composition. This review is focused on analysis of the role of EVs (mainly exosomes) in the pathogenesis of viral infection. We briefly characterize the biogenesis and molecular composition of various EV types. Then, we consider EV-mediated pro- and anti-viral mechanisms. EV secretion by infected cells can be an important factor of virus spread in target cell populations, or a protective factor limiting viral invasion. The data discussed in this review, on the effect of EV secretion by infected cells on processes in neighboring cells and on immune cells, are of high significance in the search for new therapeutic approaches and for design of new generations of vaccines.

Pannexin 2 is expressed in murine skin and promotes UVB-induced apoptosis of keratinocytes

2022 ◽  
Author(s):  
Rafael E. Sanchez-Pupo ◽  
Brooke L. O'Donnell ◽  
Danielle Johnston ◽  
Laszlo Gyenis ◽  
David W. Litchfield ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Keratinocyte Differentiation ◽  
Membrane Glycoproteins ◽  
Cellular Functions ◽  
Skin Cells ◽  
Genetic Deletion ◽  
Vitro Model ◽  
Induced Apoptosis

Pannexins (PANX) are a family of three channel-forming membrane glycoproteins expressed in the skin. Previous studies have focused on the role of PANX1 and PANX3 in the regulation of cellular functions in skin cells while PANX2, the largest member of this protein family, has not been investigated. In the current study, we explored the temporal PANX2 expression in murine skin and found that one Panx2 splice variant ( Panx2-202) tends to be more abundant at the protein level and is continuously expressed in developed skin. PANX2 was detected in the suprabasal layers of the mouse epidermis and upregulated in an in vitro model of rat epidermal keratinocyte differentiation. Furthermore, we showed that in apoptotic rat keratinocytes, upon UVB-induced caspase-3/7 activation, ectopically overexpressed PANX2 is cleaved in its C-terminal domain at D416 residue without increasing the apoptotic rate measured by caspase-3/7 activation. Notably, CRISPR-Cas9-mediated genetic deletion of rat Panx2 delays but does not impair caspase-3/7 activation and cytotoxicity in UVB-irradiated keratinocytes. We propose that endogenous PANX2 expression in keratinocytes promotes cell death after UVB insult and may contribute to skin homeostasis.

Role of melatonin in regulating neurogenesis: Implications for the neurodegenerative pathology and analogous therapeutics for Alzheimer’s disease

2020 ◽  
Vol 3 (2) ◽  
pp. 216-242 ◽  
Author(s):  
Mayuri Shukla ◽  
Areechun Sotthibundhu ◽  
Piyarat Govitrapong
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adult Neurogenesis ◽  
Adult Brain ◽  
Therapeutic Approaches ◽  
Therapeutic Implications ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Progenitor Cell Proliferation

The revelation of adult brain exhibiting neurogenesis has established that the brain possesses great plasticity and that neurons could be spawned in the neurogenic zones where hippocampal adult neurogenesis attributes to learning and memory processes. With strong implications in brain functional homeostasis, aging and cognition, various aspects of adult neurogenesis reveal exuberant mechanistic associations thereby further aiding in facilitating the therapeutic approaches regarding the development of neurodegenerative processes in Alzheimer’s Disease (AD). Impaired neurogenesis has been significantly evident in AD with compromised hippocampal function and cognitive deficits. Melatonin the pineal indolamine augments neurogenesis and has been linked to AD development as its levels are compromised with disease progression. Here, in this review, we discuss and appraise the mechanisms via which melatonin regulates neurogenesis in pathophysiological conditions which would unravel the molecular basis in such conditions and its role in endogenous brain repair. Also, its components as key regulators of neural stem and progenitor cell proliferation and differentiation in the embryonic and adult brain would aid in accentuating the therapeutic implications of this indoleamine in line of prevention and treatment of AD.   

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