scholarly journals p63+Krt5+ Basal Cells are Increased in the Squamous Metaplastic Epithelium of Patients with Radiation-induced Chronic Rhinosinusitis

2020 ◽  
Author(s):  
Hongming Huang ◽  
Kai Sen Tan ◽  
Suizi Zhou ◽  
Tian Yuan ◽  
Jing Liu ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Squamous Metaplasia ◽  
Inferior Turbinate ◽  
Nasal Epithelium ◽  
Basal Cells ◽  
Airway Epithelial ◽  
Pathologic Feature ◽  
Metaplastic Epithelium ◽  
Radiation Induced ◽  
Epithelial Remodeling

Abstract Background: Squamous metaplasia (SM) is an irreversible form of airway epithelial remodeling. Hyperproliferation of basal cells was observed in squamous metaplastic epithelium of chronically inflamed airway. However, the association of such aberrant proliferation of basal cells with SM in the nasal epithelium after radiation damage remains unclear. The aim of this study was to investigate SM and accompanying levels of p63+Krt5+ (basal cell markers) cells in the nasal epithelium of patients with radiation-induced chronic rhinosinusitis (CRSr) and patients with chronic rhinosinusitis without nasal polyps (CRSsNP) compared to healthy controls.Methods: We assessed the prevalence of SM and the expression of p63+, Krt5+, p63+Krt5+, and Ki67+ cells through immunofluorescence(IF) staining of the inferior turbinate (IT) tissues from patients with CRSr (n = 36) , CRSsNP (n = 33) and controls (n = 28).Results: The prevalence of SM and the number of p63+Krt5+ cells were both significantly increased in patients with CRSr compared to patients with CRSsNP and controls. The number of Ki67+ cells were both significantly increased in patients with CRSr and CRSsNP compared to controls, but the ratio of Ki67+ cells to p63+Krt5+ cells was significantly lower in patients with CRSr compared to patients with CRSsNP. In patients with CRSr, an increased number of p63+Krt5+ basal cells was observed in SM epithelium compared to non-SM epithelium.Conclusion: SM is increased in the nasal epithelium of patients with CRSr, in which aberrant levels of p63+Krt5+ basal cells serves as an important pathologic feature in the squamous metaplastic epithelium.

scholarly journals p63+Krt5+ basal cells are increased in the squamous metaplastic epithelium of patients with radiation-induced chronic Rhinosinusitis

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Hongming Huang ◽  
Kai Sen Tan ◽  
Suizi Zhou ◽  
Tian Yuan ◽  
Jing Liu ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Squamous Metaplasia ◽  
Inferior Turbinate ◽  
Nasal Epithelium ◽  
Basal Cells ◽  
Airway Epithelial ◽  
Pathologic Feature ◽  
Metaplastic Epithelium ◽  
Radiation Induced ◽  
Epithelial Remodeling

Abstract Background Squamous metaplasia (SM) is an irreversible form of airway epithelial remodeling. Hyperproliferation of basal cells was observed in squamous metaplastic epithelium of chronically inflamed airway. However, the association of such aberrant proliferation of basal cells with SM in the nasal epithelium after radiation damage remains unclear. The aim of this study was to investigate SM and accompanying levels of p63+Krt5+ (basal cell markers) cells in the nasal epithelium of patients with radiation-induced chronic rhinosinusitis (CRSr) and patients with chronic rhinosinusitis without nasal polyps (CRSsNP) compared to healthy controls. Methods We assessed the prevalence of SM and the expression of p63+, Krt5+, p63+Krt5+, and Ki67+ cells through immunofluorescence(IF) staining of the inferior turbinate (IT) tissues from patients with CRSr (n = 36), CRSsNP (n = 33) and controls (n = 28). Results The prevalence of SM and the number of p63+Krt5+ cells were both significantly increased in patients with CRSr compared to patients with CRSsNP and controls. The number of Ki67+ cells were both significantly increased in patients with CRSr and CRSsNP compared to controls, but the ratio of Ki67+ cells to p63+Krt5+ cells was significantly lower in patients with CRSr compared to patients with CRSsNP. In patients with CRSr, an increased number of p63+Krt5+ basal cells was observed in SM epithelium compared to non-SM epithelium. Conclusion SM is increased in the nasal epithelium of patients with CRSr, in which aberrant levels of p63+Krt5+ basal cells serves as an important pathologic feature in the squamous metaplastic epithelium.

scholarly journals Altered polarization of PAR-2 signaling during airway epithelial remodeling

2020 ◽  
Author(s):  
Ryan M. Carey ◽  
Jenna R. Freund ◽  
Benjamin M. Hariri ◽  
Nithin D. Adappa ◽  
James N. Palmer ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Cigarette Smoke ◽  
Squamous Metaplasia ◽  
Airway Epithelial ◽  
Ciliated Cells ◽  
Cigarette Smoke Condensate ◽  
Squamous Cells ◽  
Epithelial Morphology ◽  
Epithelial Remodeling ◽  
Air Liquid Interface

ABSTRACTBackgroundProtease-activated receptor 2 (PAR-2) is activated by proteases involved in allergy and triggers airway epithelial secretion and inflammation. PAR-2 is normally expressed basolaterally in differentiated nasal ciliated cells.ObjectiveWe tested if epithelial remodeling during diseases characterized by loss of cilia and squamous metaplasia may alter PAR-2 polarization.MethodsEndogenous PAR-2 responses were measured by live cell calcium and cilia imaging, measurement of fluid secretion, and quantification of cytokines. We utilized airway squamous cell lines, primary differentiated air-liquid interface cultures, and tissue explants. Cells were exposed to disease-related modifiers that alter epithelial morphology, including IL-13, cigarette smoke condensate, and retinoic acid deficiency. We used concentrations and exposure times that altered epithelial morphology without causing breakdown of the epithelial barrier, likely reflecting early disease states.ResultsPAR-2 signaling in airway squamous cells activated calcium and inflammatory responses. Squamous cells cultured at air liquid interface (ALI) responded to PAR-2 agonists applied both apically and basolaterally. Primary well-differentiated nasal epithelial ALI cultures responded only to basolateral PAR-2 stimulation. Primary cultures exposed to IL-13, cigarette smoke condensate, or reduced retinoic acid responded to both apical and basolateral PAR-2 stimulation. Nasal polyp tissue, but not control middle turbinate, exhibited apical calcium responses to PAR-2 stimulation. However, isolated ciliated cells from both polyp and turbinate maintained basolateral PAR-2 polarization.ConclusionsSquamous metaplasia and/or loss of cilia enhances apical PAR-2 responses. Altered PAR-2 polarization in dedifferentiated or remodeled epithelia may contribute to increased sensitivity to inhaled protease allergens in inflammatory airway diseases.

scholarly journals Polarization of protease-activated receptor 2 (PAR-2) signaling is altered during airway epithelial remodeling and deciliation

2020 ◽  
Vol 295 (19) ◽  
pp. 6721-6740 ◽  
Author(s):  
Ryan M. Carey ◽  
Jenna R. Freund ◽  
Benjamin M. Hariri ◽  
Nithin D. Adappa ◽  
James N. Palmer ◽  
...  
Keyword(s):  
Nasal Polyps ◽  
Squamous Metaplasia ◽  
Beat Frequency ◽  
Primary Cultures ◽  
Middle Turbinate ◽  
Airway Epithelial ◽  
Ciliated Cells ◽  
Epithelial Morphology ◽  
Epithelial Remodeling ◽  
Protease Activated Receptor 2

Protease-activated receptor 2 (PAR-2) is activated by secreted proteases from immune cells or fungi. PAR-2 is normally expressed basolaterally in differentiated nasal ciliated cells. We hypothesized that epithelial remodeling during diseases characterized by cilial loss and squamous metaplasia may alter PAR-2 polarization. Here, using a fluorescent arrestin assay, we confirmed that the common fungal airway pathogen Aspergillus fumigatus activates heterologously-expressed PAR-2. Endogenous PAR-2 activation in submerged airway RPMI 2650 or NCI–H520 squamous cells increased intracellular calcium levels and granulocyte macrophage–colony-stimulating factor, tumor necrosis factor α, and interleukin (IL)-6 secretion. RPMI 2650 cells cultured at an air–liquid interface (ALI) responded to apically or basolaterally applied PAR-2 agonists. However, well-differentiated primary nasal epithelial ALIs responded only to basolateral PAR-2 stimulation, indicated by calcium elevation, increased cilia beat frequency, and increased fluid and cytokine secretion. We exposed primary cells to disease-related modifiers that alter epithelial morphology, including IL-13, cigarette smoke condensate, and retinoic acid deficiency, at concentrations and times that altered epithelial morphology without causing breakdown of the epithelial barrier to model early disease states. These altered primary cultures responded to both apical and basolateral PAR-2 stimulation. Imaging nasal polyps and control middle turbinate explants, we found that nasal polyps, but not turbinates, exhibit apical calcium responses to PAR-2 stimulation. However, isolated ciliated cells from both polyps and turbinates maintained basolateral PAR-2 polarization, suggesting that the calcium responses originated from nonciliated cells. Altered PAR-2 polarization in disease-remodeled epithelia may enhance apical responses and increase sensitivity to inhaled proteases.

Distinct Patterns of Tissue Remodeling and Their Prognostic Role in Chronic Rhinosinusitis

ORL ◽  
2021 ◽  
pp. 1-7
Author(s):  
Ho Yun Lee ◽  
Jung-Soo Pyo ◽  
Su Jin Kim
Keyword(s):  
Chronic Rhinosinusitis ◽  
Structural Changes ◽  
Squamous Metaplasia ◽  
Tissue Remodeling ◽  
Sinus Surgery ◽  
Prognostic Role ◽  
High Power Field ◽  
Tissue Eosinophilia ◽  
Allergy Test ◽  
Stromal Edema

<b><i>Introduction:</i></b> Tissue remodeling refers to structural changes that occur in damaged tissue and is associated with disease severity in asthma. However, the characteristics of tissue remodeling and its prognostic role in chronic rhinosinusitis (CRS) remain unclear. In this report, we evaluated the clinical implications of tissue remodeling in CRS. <b><i>Methods:</i></b> We performed a retrospective cohort study of adult patients who underwent endoscopic sinus surgery for bilateral CRS. The histopathology of sinus mucosa was determined by evaluating the inflammatory cell count and tissue remodeling markers (squamous metaplasia, subepithelial gland proliferation, basement membrane [BM] thickening, stromal edema, and fibrosis). Eosinophilic CRS (ECRS) was defined as an eosinophil count &#x3e;15/high-power field in the biopsied tissue. Patient characteristics, allergy test grade, preoperative Lund-Mackay score (LMS), and pre- and postoperative Lund-Kennedy scores (LKSs) were analyzed. <b><i>Results:</i></b> Of the identified patients, 59.1% were classified as ECRS and the remaining 40.9% as non-ECRS. Regarding tissue remodeling markers, stromal edema was seen in 90.9%, BM thickening in 63.6%, and stromal fibrosis in 34.1% of patients. In cases with stromal edema and BM thickening, greater tissue eosinophilia was observed, while stromal fibrosis decreased tissue eosinophilia (<i>p</i> &#x3c; 0.05). Prognostically, subepithelial gland proliferation alone was an independent risk factor for poor postoperative endoscopic findings (odds ratio: 8.250, 95% confidence interval: 1.128–60.319, <i>p</i> = 0.038). <b><i>Conclusions:</i></b> Tissue eosinophilia was commonly associated with BM thickening and stromal edema. Subepithelial gland proliferation predicted a poor surgical prognosis in CRS. These findings imply that tissue remodeling provides additional information not only on the CRS endotype but also on the postsurgical prognosis.

Assessment of Biomarker Heterogeneity in Sinus Versus Inferior Turbinate Tissue in Patients Without Chronic Rhinosinusitis

2021 ◽  
pp. 194589242110128
Author(s):  
Taylor R. Carle ◽  
Tara J. Wu ◽  
Vivian Wung ◽  
Jeffrey D. Suh ◽  
Marilene B. Wang ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Sphenoid Sinus ◽  
Inferior Turbinate ◽  
Optimal Choice ◽  
Control Specimen ◽  
Luminex Assay ◽  
Healthy Control ◽  
History Of ◽  
Sinonasal Mucosa ◽  
Sinus Mucosa

Background Currently, no consensus exists on the appropriate control specimen site to utilize in studies evaluating for biomarkers in chronic rhinosinusitis (CRS). Studies thus far have utilized tissue from various anatomic sites despite regional heterogeneity. Objective We set out to quantify the differences in biomarker levels present in inferior turbinate versus sphenoid sinus mucosa in paired healthy control patients. We hypothesize that statistically significant differences in cytokine/chemokine expression exist between these two distinct sites. Methods A 38-plex commercially available cytokine/chemokine Luminex Assay was performed on 54 specimens encompassing paired inferior turbinate and sphenoid sinus mucosa samples from 27 patients undergoing endoscopic anterior skull base surgery. Patients with a history of CRS were excluded. Paired sample t-tests and Fisher’s exact tests were performed. Results Twenty-seven patients were included in the study, including 10 male and 17 female patients with an average age of 48 years. The following 8 biomarkers had statistically significant concentration differences between inferior turbinate mucosa and sphenoid mucosa sites: Flt-3L, Fractalkine, IL-12p40, IL-1Ra, IP-10, MCP-1, MIP-1β, and VEGF, with all P-values <0.01. Conclusion No consensus exists regarding the optimal choice of control specimen for CRS research. We present statistically significant quantitative differences in biomarker levels between paired inferior turbinate and sphenoid mucosa samples. This confirms the presence of heterogeneity between different subsites of sinonasal mucosa and highlights the need for standardization in future CRS research.

scholarly journals Histologic Aspect of the Curved Vomerine Mucosa in Cleft Lip and Palate

2021 ◽  
pp. 105566562110314
Author(s):  
Benito K. Benitez ◽  
Andrzej Brudnicki ◽  
Prasad Nalabothu ◽  
Jeannette A. von Jackowski ◽  
Elisabeth Bruder ◽  
...  
Keyword(s):  
Nasal Mucosa ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Squamous Metaplasia ◽  
Periodic Acid ◽  
Surgical Techniques ◽  
Basal Cells ◽  
Periodic Acid Schiff ◽  
Tissue Samples ◽  
Nasal Floor

Background: Common surgical techniques aim to turn the entire vomerine mucosa with vomer flaps either to the oral side or to the nasal side. The latter approach is widely performed due to the similarity in color to the nasal mucosa. However, we lack a histologic description of the curved vomerine mucosa in cleft lip and palate malformations. Methods: We histologically examined an excess of curved vomerine mucosa in 8 patients using hematoxylin–eosin, periodic acid–Schiff, Elastin van Gieson, and Alcian blue stains. Tissue samples were obtained during surgery at 8 months of age. Results: Our histological analysis of the mucoperiosteum overlying the curved vomer revealed characteristics consistent with those of an oral mucosa or a squamous metaplasia of the nasal mucosa, as exhibited by a stratified squamous epithelium containing numerous seromucous glands. Some areas showed a palisaded arrangement of the basal cells compatible with metaplasia of respiratory epithelium, but no goblet cells or respiratory cilia were identified. Abundant fibrosis and rich vascularity were present. Conclusion: The vomer mucosa showed no specific signs of nasal mucosa. These findings should be considered in presurgical cleft orthopedics and palatal surgery for further refinement. Shifting the vomer mucosa according to a fixed physiologic belief should not overrule other important aspects of cleft repair such as primary healing and establishing optimal form and function of palatal roof and nasal floor.

scholarly journals Cellular basis of urothelial squamous metaplasia

2005 ◽  
Vol 171 (5) ◽  
pp. 835-844 ◽  
Author(s):  
Feng-Xia Liang ◽  
Maarten C. Bosland ◽  
Hongying Huang ◽  
Rok Romih ◽  
Solange Baptiste ◽  
...  
Keyword(s):  
Vitamin A ◽  
Vitamin A Deficiency ◽  
Squamous Metaplasia ◽  
Culture Conditions ◽  
Growth Potential ◽  
Basal Cells ◽  
Cellular Basis ◽  
Proximal Urethra

Although the epithelial lining of much of the mammalian urinary tract is known simply as the urothelium, this epithelium can be divided into at least three lineages of renal pelvis/ureter, bladder/trigone, and proximal urethra based on their embryonic origin, uroplakin content, keratin expression pattern, in vitro growth potential, and propensity to keratinize during vitamin A deficiency. Moreover, these cells remain phenotypically distinct even after they have been serially passaged under identical culture conditions, thus ruling out local mesenchymal influence as the sole cause of their in vivo differences. During vitamin A deficiency, mouse urothelium form multiple keratinized foci in proximal urethra probably originating from scattered K14-positive basal cells, and the keratinized epithelium expands horizontally to replace the surrounding normal urothelium. These data suggest that the urothelium consists of multiple cell lineages, that trigone urothelium is closely related to the urothelium covering the rest of the bladder, and that lineage heterogeneity coupled with cell migration/replacement form the cellular basis for urothelial squamous metaplasia.

scholarly journals A novel role for bone marrow-derived cells to recover damaged keratinocytes from radiation-induced injury

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Junko Okano ◽  
Yuki Nakae ◽  
Takahiko Nakagawa ◽  
Miwako Katagi ◽  
Tomoya Terashima ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Underlying Mechanism ◽  
Basal Cells ◽  
Barrier Dysfunction ◽  
Skin Injury ◽  
Accelerated Proliferation ◽  
Radiation Induced ◽  
Bone Marrow Derived Cells ◽  
Injury Recovery

AbstractExposure to moderate doses of ionizing radiation (IR), which is sufficient for causing skin injury, can occur during radiation therapy as well as in radiation accidents. Radiation-induced skin injury occasionally recovers, although its underlying mechanism remains unclear. Moderate-dose IR is frequently utilized for bone marrow transplantation in mice; therefore, this mouse model can help understand the mechanism. We had previously reported that bone marrow-derived cells (BMDCs) migrate to the epidermis-dermis junction in response to IR, although their role remains unknown. Here, we investigated the role of BMDCs in radiation-induced skin injury in BMT mice and observed that BMDCs contributed to skin recovery after IR-induced barrier dysfunction. One of the important mechanisms involved the action of CCL17 secreted by BMDCs on irradiated basal cells, leading to accelerated proliferation and recovery of apoptosis caused by IR. Our findings suggest that BMDCs are key players in IR-induced skin injury recovery.

Sign in / Sign up

Export Citation Format

Share Document