Reticular Basement Membrane Thickness Is Associated with Growth- and Fibrosis-Promoting Airway Transcriptome Profile-Study in Asthma Patients

Airway remodeling in asthma is characterized by reticular basement membrane (RBM) thickening, likely related to epithelial structural and functional changes. Gene expression profiling of the airway epithelium might identify genes involved in bronchial structural alterations. We analyzed bronchial wall geometry (computed tomography (CT)), RBM thickness (histology), and the bronchial epithelium transcriptome profile (gene expression array) in moderate to severe persistent (n = 21) vs. no persistent (n = 19) airflow limitation asthmatics. RBM thickness was similar in the two studied subgroups. Among the genes associated with increased RBM thickness, the most essential were those engaged in cell activation, proliferation, and growth (e.g., CDK20, TACC2, ORC5, and NEK5) and inhibiting apoptosis (e.g., higher mRNA expression of RFN34, BIRC3, NAA16, and lower of RNF13, MRPL37, CACNA1G). Additionally, RBM thickness correlated with the expression of genes encoding extracellular matrix (ECM) components (LAMA3, USH2A), involved in ECM remodeling (LTBP1), neovascularization (FGD5, HPRT1), nerve functioning (TPH1, PCDHGC4), oxidative stress adaptation (RIT1, HSP90AB1), epigenetic modifications (OLMALINC, DNMT3A), and the innate immune response (STAP1, OAS2). Cluster analysis revealed that genes linked with RBM thickness were also related to thicker bronchial walls in CT. Our study suggests that the pro-fibrotic profile in the airway epithelial cell transcriptome is associated with a thicker RBM, and thus, may contribute to asthma airway remodeling.

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Application of Euclidean distance mapping for assessment of basement membrane thickness distribution in asthma

Journal of Applied Physiology ◽

10.1152/japplphysiol.00171.2017 ◽

2017 ◽

Vol 123 (2) ◽

pp. 473-481 ◽

Cited By ~ 2

Author(s):

Leila Mostaco-Guidolin ◽

Soheil Hajimohammadi ◽

Dragoş M. Vasilescu ◽

Tillie-Louise Hackett

Keyword(s):

Basement Membrane ◽

Airway Epithelium ◽

Lung Diseases ◽

Euclidean Distance ◽

Airway Remodeling ◽

Thickness Distribution ◽

Membrane Thickness ◽

Small Airways ◽

Basement Membrane Thickness ◽

Distance Mapping

Abnormal thickening of the airway basement membrane is one of the hallmarks of airway remodeling in asthma. The present protocols for measuring the basement membrane involve the use of stained tissue sections and measurements of the basement membrane thickness at certain intervals, followed by the calculation of the geometric mean thickness for each airway. This report describes an automated, unbiased approach which uses color segmentation to identify structures of interest on stained sections and Euclidean distance mapping to measure the thickness distribution of airway structures. This method was applied to study the thickness distribution of the basement membrane and airway epithelium in lungs donated for research from seven nonasthmatic and eight asthmatic age- and sex-matched donors. A total of 60 airways were assessed. We report that the thickness and thickness distribution of the basement membrane and airway epithelium are increased in large and small airways of asthmatics compared with nonasthmatics. Using this method we were able to demonstrate the heterogeneity in the thickness of the basement membrane and airway epithelium within individual airways of asthmatic subjects. This new computational method enables comprehensive and objective quantification of airway structures, which can be used to quantify heterogeneity of airway remodeling in obstructive lung diseases such as asthma and chronic obstructive pulmonary disease. NEW & NOTEWORTHY The described application of Euclidean distance mapping provides an unbiased approach to study the extent and thickness distribution of changes in tissue structures. This approach will enable researchers to use computer-aided analysis of structural changes within lung tissue to understand the heterogeneity of airway remodeling in lung diseases.

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Basement membrane thickness in muscle capillaries of normal and spontaneously diabetic Macaca nigra

Diabetes ◽

10.2337/diabetes.24.2.201 ◽

1975 ◽

Vol 24 (2) ◽

pp. 201-206 ◽

Cited By ~ 11

Author(s):

C. F. Howard

Keyword(s):

Basement Membrane ◽

Membrane Thickness ◽

Basement Membrane Thickness ◽

Macaca Nigra ◽

Muscle Capillaries

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Editorial Comment from Dr Hotta to Clinical impact of glomerular basement membrane thickness on post‐donation renal function in living donors

International Journal of Urology ◽

10.1111/iju.13858 ◽

2018 ◽

Vol 26 (2) ◽

pp. 311-311

Author(s):

Kiyohiko Hotta

Keyword(s):

Renal Function ◽

Basement Membrane ◽

Editorial Comment ◽

Glomerular Basement Membrane ◽

Living Donors ◽

Clinical Impact ◽

Membrane Thickness ◽

Basement Membrane Thickness ◽

Glomerular Basement Membrane Thickness

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A semi-automatic algorithm for measurement of basement membrane thickness in kidneys in electron microscopy images

Computer Methods and Programs in Biomedicine ◽

10.1016/j.cmpb.2009.07.002 ◽

2010 ◽

Vol 97 (3) ◽

pp. 223-231 ◽

Cited By ~ 5

Author(s):

Hai-Shan Wu ◽

Steven Dikman ◽

Joan Gil

Keyword(s):

Electron Microscopy ◽

Basement Membrane ◽

Membrane Thickness ◽

Basement Membrane Thickness ◽

Microscopy Images ◽

Automatic Algorithm

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Microvascular Response to Tissue Injury and Capillary Ultrastructure in the Foot Skin of Type I Diabetic Patients

Clinical Science ◽

10.1042/cs0890467 ◽

1995 ◽

Vol 89 (5) ◽

pp. 467-474 ◽

Cited By ~ 39

Author(s):

G. Rayman ◽

R. A. Malik ◽

A. K. Sharma ◽

J. L. Day

Keyword(s):

Basement Membrane ◽

Light And Electron Microscopy ◽

Microvascular Blood Flow ◽

Diabetic Patients ◽

Membrane Thickness ◽

Type I ◽

Basement Membrane Thickness ◽

Doppler Flowmetry ◽

Hyperaemic Response ◽

Capillary Size

1. Microvascular blood flow responses to injury and capillary ultrastructure were assessed by laser Doppler flowmetry and detailed light and electron microscopy respectively in skin biopsied from 28 patients with insulin-dependent diabetes and 17 control subjects. 2. The hyperaemic response induced by biopsy (P < 0.001) and heating to 44°C (P < 0.001) was significantly lower in the diabetic patients and showed progressive impairment with the severity of complications (P < 0.001). 3. Skin capillary basement membrane thickness was significantly increased in the diabetic patients (P < 0.001) and also increased with the severity of complications (P < 0.002). Both the luminal area (P < 0.001) and the endothelial cell outer perimeter (P < 0.002), measures of luminal and capillary size, respectively, were significantly reduced in all diabetic patients. 4. Basement membrane thickness was related significantly to the impaired hyperaemic response to both biopsy (P < 0.01) and thermal injury (P < 0.01). 5. Our findings support the hypothesis that structural abnormalities, which are characterized by an early reduction in capillary size and later thickening of basement membrane, form an important mechanism for the impaired hyperaemic response in diabetic patients.

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The Relationship of Reticular Basement Membrane Thickness to Airway Wall Remodeling in Asthma

American Journal of Respiratory and Critical Care Medicine ◽

10.1164/rccm.2108069 ◽

2002 ◽

Vol 166 (12) ◽

pp. 1590-1595 ◽

Cited By ~ 100

Author(s):

Alan L. James ◽

Peta S. Maxwell ◽

Gladys Pearce-Pinto ◽

John G. Elliot ◽

Neil G. Carroll

Keyword(s):

Basement Membrane ◽

Membrane Thickness ◽

Airway Wall ◽

Basement Membrane Thickness ◽

Relationship Of ◽

The Relationship

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Dependency of Muscle Capillary Basement Membrane Thickness on the Duration of Diabetes

Diabetes Care ◽

10.2337/diacare.2.6.472 ◽

1979 ◽

Vol 2 (6) ◽

pp. 472-478 ◽

Cited By ~ 13

Author(s):

E. A. Siess ◽

H. E. Nathke ◽

T. Dexel ◽

M. Haslbeck ◽

H. Mehnert ◽

...

Keyword(s):

Basement Membrane ◽

Membrane Thickness ◽

Basement Membrane Thickness ◽

Duration Of Diabetes ◽

Capillary Basement Membrane

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Influences of physical conditioning and deconditioning on coronary vasculature of dogs

Journal of Applied Physiology ◽

10.1152/jappl.1978.45.4.619 ◽

1978 ◽

Vol 45 (4) ◽

pp. 619-625 ◽

Cited By ~ 67

Author(s):

H. L. Wyatt ◽

J. Mitchell

Keyword(s):

Basement Membrane ◽

Capillary Density ◽

Cross Sectional Area ◽

Membrane Thickness ◽

Physical Conditioning ◽

Sectional Area ◽

Circumflex Artery ◽

Cross Sectional ◽

Coronary Vasculature ◽

Basement Membrane Thickness

To investigate the effects of physical conditioning and deconditioning on the coronary vasculature, eight dogs were exercised by treadmill running. Five dogs were deconditioned by confinement in cages following the conditioning period. A technique was developed and validated for measuring circumflex coronary artery diameter from magnified projections of standardized coronary angiograms. Myocardial capillary density, perimeter, and basement membrane thickness were determined from electron microscopy of serial ventricular septal biopsy samples. Physical conditioning caused a small but statistically significant increase in cross-sectional area of the circumflex artery. Although physical conditioning caused no statistically significant changes in the myocardial capillaries, trends were apparent for increases in density and perimeter of myocardial capillaries and a decrease in basement membrane thickness. Physical deconditioning caused statistically significant reductions in cross-sectional area of the circumflex artery and in myocardial capillary density but little change in perimeter or basement membrane thickness of myocardial capillaries. The results suggest that physical conditioning may be associated with an improvement in coronary vascular capacity which may regress rapidly with deconditioning.

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