scholarly journals Transient Effects of Cyclophosphamide on Basal Cell Proliferation of Olfactory Epithelia

2020 ◽  
Vol 45 (7) ◽  
pp. 549-561
Author(s):  
Kyle B Joseph ◽  
Nora Awadallah ◽  
Eugene R Delay ◽  
Rona J Delay
Keyword(s):  
Cell Proliferation ◽  
Side Effects ◽  
Basal Cell ◽  
Vomeronasal Organ ◽  
Cell Renewal ◽  
Basal Cells ◽  
Transient Effects ◽  
Main Olfactory Epithelium ◽  
Immunohistochemical Markers ◽  
Horizontal Basal Cells

Abstract Cancer is often treated with broad-spectrum cytotoxic drugs that not only eradicate cancerous cells but also have detrimental side effects. One of these side effects, disruption of the olfactory system, impedes a patient’s ability to smell, perceive flavor, and ultimately may interfere with their nutritional intake and recovery from cancer. Recent studies reported that the chemotherapy drug, cyclophosphamide (CYP), can damage gustatory epithelia and disrupt cell proliferation in olfactory epithelia. In this study, we asked if CYP altered globose and horizontal basal cell proliferation in the murine main olfactory epithelium (MOE) and vomeronasal organ (VNO). We used antibodies for Ki67, a marker strictly associated with cell proliferation, and Keratin 5, a marker for the cytoskeleton of horizontal basal cells. Our results revealed a significant CYP-induced decrease in the number of proliferative cells in both epithelia, especially globose basal cells in the MOE, within the first 1–2 days postinjection. Recovery of cell renewal was apparent 6 days after injection. The immunohistochemical markers showed significantly higher levels of globose and horizontal basal cell proliferation in CYP-injected mice at 14 and 30 days postinjection compared with control mice. The prolonged proliferative activation of globose and horizontal basal cells suggests that, besides altering proliferation of olfactory epithelia, the epithelial substrate needed for successful cell renewal may be adversely affected by CYP.

scholarly journals Cyclophosphamide has Long-Term Effects on Proliferation in Olfactory Epithelia

2019 ◽  
Vol 45 (2) ◽  
pp. 97-109
Author(s):  
Nora Awadallah ◽  
Kara Proctor ◽  
Kyle B Joseph ◽  
Eugene R Delay ◽  
Rona J Delay
Keyword(s):  
Cell Proliferation ◽  
Vomeronasal Organ ◽  
Cell Renewal ◽  
Loss Of Function ◽  
Long Term Effects ◽  
Proliferating Cells ◽  
Taste System ◽  
Main Olfactory Epithelium ◽  
Sensory Layer ◽  
Chemotherapy Patients

Abstract Chemotherapy patients often experience chemosensory changes during and after drug therapy. The chemotherapy drug, cyclophosphamide (CYP), has known cytotoxic effects on sensory and proliferating cells of the taste system. Like the taste system, cells in the olfactory epithelia undergo continuous renewal. Therefore, we asked if a single injection of 75 mg/kg CYP would affect cell proliferation in the anterior dorsomedial region of the main olfactory epithelium (MOE) and the vomeronasal organ (VNO) from 0 to 125 days after injection. Both epithelia showed a decrease in Ki67-labeled cells compared to controls at day 1 and no Ki67+ cells at day 2 postinjection. In the sensory layer of the MOE, cell proliferation began to recover 4 days after CYP injection and by 6 days, the rate of proliferation was significantly greater than controls. Ki67+ cells peaked 30 days postinjection, then declined to control levels at day 45. Similar temporal sequences of initial CYP-induced suppression of cell proliferation followed by elevated rates peaking 30–45 days postinjection were seen in the sustentacular layer of the MOE and all 3 areas (sensory, sustentacular, marginal) of the VNO. CYP affected proliferation in the sensory layer of the MOE more than the sustentacular layer and all 3 areas of the VNO. These findings suggest that chemotherapy involving CYP is capable of affecting cell renewal of the olfactory system and likely contributes to clinical loss of function during and after chemotherapy.

scholarly journals The Microvillar and Solitary Chemosensory Cells as the Novel Targets of Infection of SARS-CoV-2 in Syrian Golden Hamsters

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1653
Author(s):  
Jin-Seok Seo ◽  
Sun-Woo Yoon ◽  
Seung-Hyeon Hwang ◽  
Sung-Min Nam ◽  
Sang-Soep Nahm ◽  
...  
Keyword(s):  
Vomeronasal Organ ◽  
Inflammatory Cells ◽  
Receptor Protein ◽  
Basal Cells ◽  
Main Olfactory Epithelium ◽  
Golden Hamsters ◽  
Olfactory Loss ◽  
Syrian Golden Hamsters ◽  
Solitary Chemosensory Cells ◽  
Cellular Components

Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019, suffer from respiratory and non-respiratory symptoms. Among these symptoms, the loss of smell has attracted considerable attention. The objectives of this study were to determine which cells are infected, what happens in the olfactory system after viral infection, and how these pathologic changes contribute to olfactory loss. For this purpose, Syrian golden hamsters were used. First, we verified the olfactory structures in the nasal cavity of Syrian golden hamsters, namely the main olfactory epithelium, the vomeronasal organ, and their cellular components. Second, we found angiotensin-converting enzyme 2 expression, a receptor protein of SARS-CoV-2, in both structures and infections of supporting, microvillar, and solitary chemosensory cells. Third, we observed pathological changes in the infected epithelium, including reduced thickness of the mucus layer, detached epithelia, indistinct layers of epithelia, infiltration of inflammatory cells, and apoptotic cells in the overall layers. We concluded that a structurally and functionally altered microenvironment influences olfactory function. We observed the regeneration of the damaged epithelium, and found multilayers of basal cells, indicating that they were activated and proliferating to reconstitute the injured epithelium.

scholarly journals Epidermal growth factor receptor activity is necessary for mouse basal cell proliferation

2014 ◽  
Vol 307 (10) ◽  
pp. L800-L810 ◽  
Author(s):  
Heather M. Brechbuhl ◽  
Bilan Li ◽  
Russell W. Smith ◽  
Susan D. Reynolds
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Basal Cell ◽  
Basal Cells ◽  
Epithelial Repair ◽  
Epidermal Growth ◽  
Proliferation In Vitro

ERB family receptors (EGFR, ERB-B2, ERB-B3, and ERB-B4) regulate epithelial cell function in many tissue types. In the human airway epithelium, changes in ERB receptor expression are associated with epithelial repair defects. However, the specific role(s) played by ERB receptors in repair have not been determined. We aimed to determine whether ERB receptors regulate proliferation of the tracheobronchial progenitor, the basal cell. Receptor tyrosine kinase arrays were used to evaluate ERB activity in normal and naphthalene (NA)-injured mouse trachea and in air-liquid interface cultures. Roles for epidermal growth factor (EGF), EGFR, and ERB-B2 in basal cell proliferation were evaluated in vitro. NA injury and transgenic expression of an EGFR-dominant negative (DN) receptor were used to evaluate roles for EGFR signaling in vivo. EGFR and ERB-B2 were active in normal and NA-injured trachea and were the only active ERB receptors detected in proliferating basal cells in vitro. EGF was necessary for basal cell proliferation in vitro. The EGFR inhibitor, AG1478, decreased proliferation by 99, and the Erb-B2 inhibitor, AG825, decreased proliferation by ∼66%. In vivo, EGFR-DN expression in basal cells significantly decreased basal cell proliferation after NA injury. EGF and EGFR are necessary for basal cell proliferation. The EGFR/EGFR homo- and the EGFR/ERB-B2 heterodimer account for ∼34 and 66%, respectively, of basal cell proliferation in vitro. Active EGFR is necessary for basal cell proliferation after NA injury. We conclude that EGFR activation is necessary for mouse basal cell proliferation and normal epithelial repair.

scholarly journals Sensing of apoptotic cells through Axl causes lung basal cell proliferation in inflammatory diseases

2019 ◽  
Vol 216 (9) ◽  
pp. 2184-2201 ◽  
Author(s):  
Naoya Fujino ◽  
Oliver J. Brand ◽  
David J. Morgan ◽  
Toshifumi Fujimori ◽  
Aleksander M. Grabiec ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Division ◽  
Basal Cell ◽  
Inflammatory Diseases ◽  
Ciliated Cell ◽  
Apoptotic Cells ◽  
Basal Cells ◽  
Barrier Dysfunction ◽  
Cell Hyperplasia ◽  
Cell Cycle Reentry

Epithelial cell proliferation, division, and differentiation are critical for barrier repair following inflammation, but the initial trigger for this process is unknown. Here we define that sensing of apoptotic cells by the TAM receptor tyrosine kinase Axl is a critical indicator for tracheal basal cell expansion, cell cycle reentry, and symmetrical cell division. Furthermore, once the pool of tracheal basal cells has expanded, silencing of Axl is required for their differentiation. Genetic depletion of Axl triggers asymmetrical cell division, leading to epithelial differentiation and ciliated cell regeneration. This discovery has implications for conditions associated with epithelial barrier dysfunction, basal cell hyperplasia, and continued turnover of dying cells in patients with chronic inflammatory pulmonary diseases.

scholarly journals Extracellular vesicles from human airway basal cells respond to cigarette smoke extract and affect vascular endothelial cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ashish Saxena ◽  
Matthew S. Walters ◽  
Jae-Hung Shieh ◽  
Ling-Bo Shen ◽  
Kazunori Gomi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cigarette Smoke ◽  
Extracellular Vesicles ◽  
Basal Cell ◽  
Mapk Signaling ◽  
Cigarette Smoke Extract ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Basal Cells ◽  
Human Airway

AbstractThe human airway epithelium lining the bronchial tree contains basal cells that proliferate, differentiate, and communicate with other components of their microenvironment. One method that cells use for intercellular communication involves the secretion of exosomes and other extracellular vesicles (EVs). We isolated exosome-enriched EVs that were produced from an immortalized human airway basal cell line (BCi-NS1.1) and found that their secretion is increased by exposure to cigarette smoke extract, suggesting that this stress stimulates release of EVs which could affect signaling to other cells. We have previously shown that primary human airway basal cells secrete vascular endothelial growth factor A (VEGFA) which can activate MAPK signaling cascades in endothelial cells via VEGF receptor–2 (VEGFR2). Here, we show that exposure of endothelial cells to exosome-enriched airway basal cell EVs promotes the survival of these cells and that this effect also involves VEGFR2 activation and is, at least in part, mediated by VEGFA present in the EVs. These observations demonstrate that EVs are involved in the intercellular signaling between airway basal cells and the endothelium which we previously reported. The downstream signaling pathways involved may be distinct and specific to the EVs, however, as increased phosphorylation of Akt, STAT3, p44/42 MAPK, and p38 MAPK was not seen following exposure of endothelial cells to airway basal cell EVs.

Another role for melanocytes: their importance for normal stria vascularis development in the mammalian inner ear

Development ◽  
1989 ◽  
Vol 107 (3) ◽  
pp. 453-463 ◽  
Author(s):  
K.P. Steel ◽  
C. Barkway
Keyword(s):  
Neural Crest ◽  
Basal Cell ◽  
Stria Vascularis ◽  
Normal Adult ◽  
Basal Cells ◽  
Cochlear Duct ◽  
Cell Layers ◽  
Marginal Cells ◽  
Intermediate Cells ◽  
And Function

The stria vascularis of the mammalian cochlea is composed primarily of three types of cells. Marginal cells line the lumen of the cochlear duct and are of epithelial origin. Basal cells also form a continuous layer and they may be mesodermal or derived from the neural crest. Intermediate cells are melanocyte-like cells, presumably derived from the neural crest, and are scattered between the marginal and basal cell layers. The marginal cells form extensive interdigitations with the basal and intermediate cells in the normal adult stria. The stria also contains a rich supply of blood vessels. We investigated the role of melanocytes in the stria vascularis by studying its development in a mouse mutant, viable dominant spotting, which is known to have a primary neural crest defect leading to an absence of recognisable melanocytes in the skin. Melanocytes were not found in the stria of most of the mutants examined, and from about 6 days of age onwards a reduced amount of interdigitation amongst the cells of the stria was observed. These ultrastructural anomalies were associated with strial dysfunction. In the normal adult mammal, the stria produces an endocochlear potential (EP), a resting dc potential in the endolymph in the cochlear duct, which in mice is normally about +100 mV. In our control mice, EP rose to adult levels between 6 and 16 days after birth. In most of the mutants we studied, EP was close to zero at all ages from 6 to 20 days. Melanocyte-like cells appear to be vital for normal stria vascularis development and function. They may be necessary to facilitate the normal process of interdigitation between marginal and basal cell processes at a particular stage during development, and the lack of adequate interdigitation in the mutants may be the cause of their strial dysfunction. Alternatively, melanocytes may have some direct, essential role in the production of an EP by the stria. Melanocytes may be important both for normal strial development and for the production of the EP. We believe this is the clearest demonstration yet of a role for migratory melanocytes other than their role in pigmentation.

Metastatic Basal Cell Carcinoma: Four Case Reports, Review of Literature, and Immunohistochemical Evaluation

2006 ◽  
Vol 130 (1) ◽  
pp. 45-51
Author(s):  
Diana N. Ionescu ◽  
Muammar Arida ◽  
Drazen M. Jukic
Keyword(s):  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Case Reports ◽  
Small Sample ◽  
Ki 67 ◽  
Immunohistochemical Markers ◽  
Metastatic Basal Cell Carcinoma ◽  
Metastatic Sites

Abstract Context.—Metastatic basal cell carcinoma (BCC) is relatively rare and is seldom considered a complication in the routine treatment and follow-up of patients with BCC. Although multiple studies have tried to distinguish aggressive from nonaggressive BCCs, to our knowledge, no consistent clinical, histopathologic, or immunohistochemical features have yet been reported. Objective.—To report 4 cases of metastatic BCCs and to evaluate these in addition to known nonmetastatic BCCs with specific immunostains in an attempt to find distinct morphologic or immunohistochemical patterns that could be helpful in identifying aggressive BCCs. Design.—We reviewed 4 cases of metastatic BCCs and recorded the clinical and morphologic findings. We then searched our archives for 14 cases of BCC that followed the usual nonaggressive course. We evaluated these 18 cases with immunohistochemical stains for Ki-67, p53, and bcl-2. Results.—In metastasizing BCC, Ki-67 staining was slightly higher in metastatic sites than in primary sites (average 63% and 51%, respectively). p53 was expressed in 3 of 4 primary sites and 2 of 4 metastatic sites. Bcl-2 was positive in both primary and metastatic sites in 3 of 4 cases. In the 14 cases of nonaggressive BCC, staining for Ki-67 averaged 38%, p53 was positive in 11 cases, and Bcl-2 staining was noted in 13 cases. Conclusions.—Overall, in the small sample that we evaluated, the immunohistochemical markers for Ki-67, p53, and Bcl-2 did not distinguish between metastatic and nonaggressive BCCs.

scholarly journals Hypoxia in Cell Reprogramming and the Epigenetic Regulations

2021 ◽  
Vol 9 ◽  
Author(s):  
Nariaki Nakamura ◽  
Xiaobing Shi ◽  
Radbod Darabi ◽  
Yong Li
Keyword(s):  
Cell Proliferation ◽  
Cell Fate ◽  
Tissue Regeneration ◽  
Cellular Reprogramming ◽  
Cell Reprogramming ◽  
Cell Renewal ◽  
Cellular Functions ◽  
Stem Cell Renewal ◽  
Epigenetic Regulations

Cellular reprogramming is a fundamental topic in the research of stem cells and molecular biology. It is widely investigated and its understanding is crucial for learning about different aspects of development such as cell proliferation, determination of cell fate and stem cell renewal. Other factors involved during development include hypoxia and epigenetics, which play major roles in the development of tissues and organs. This review will discuss the involvement of hypoxia and epigenetics in the regulation of cellular reprogramming and how interplay between each factor can contribute to different cellular functions as well as tissue regeneration.

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