scholarly journals 11β-HSD1 inhibition does not affect murine tumour angiogenesis but may exert a selective effect on tumour growth by modulating inflammation and fibrosis

2021 ◽  
Author(s):  
Callam T Davidson ◽  
Eileen Miller ◽  
Morwenna Muir ◽  
John C. Dawson ◽  
Martin Lee ◽  
...  
Keyword(s):  
Tumour Growth ◽  
Type I Collagen ◽  
Second Harmonic ◽  
Solid Tumours ◽  
Ductal Adenocarcinoma ◽  
Standard Diet ◽  
Type I ◽  
Murine Models ◽  
Tumour Angiogenesis ◽  
Matrix Deposition

Glucocorticoids inhibit angiogenesis by activating the glucocorticoid receptor. Inhibition of the glucocorticoid-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) reduces tissue-specific glucocorticoid action and promotes angiogenesis in murine models of myocardial infarction. Angiogenesis is important in the growth of some solid tumours. This study used murine models of squamous cell carcinoma (SCC) and pancreatic ductal adenocarcinoma (PDAC) to test the hypothesis that 11β-HSD1 inhibition promotes angiogenesis and subsequent tumour growth. SCC or PDAC cells were injected into female FVB/N or C57BL6/J mice fed either standard diet, or diet containing the 11β-HSD1 inhibitor UE2316. SCC tumours grew more rapidly in UE2316-treated mice, reaching a larger (P<0.01) final volume (0.158 ± 0.037 cm 3 ) than in control mice (0.051 ± 0.007 cm 3 ). However, PDAC tumour growth was unaffected. Immunofluorescent analysis of SCC tumours did not show differences in vessel density (CD31/alpha-smooth muscle actin) or cell proliferation (Ki67) after 11β-HSD1 inhibition, and immunohistochemistry of SCC tumours did not show changes in inflammatory cell (CD3- or F4/80-positive) infiltration. In culture, the growth/viability (assessed by live cell imaging) of SCC cells was not affected by UE2316 or corticosterone. Second Harmonic Generation microscopy showed that UE2316 reduced Type I collagen (P<0.001), whilst RNA-sequencing revealed that multiple factors involved in the innate immune/inflammatory response were reduced in UE2316-treated SCC tumours. 11β-HSD1 inhibition increases SCC tumour growth, likely via suppression of inflammatory/immune cell signalling and extracellular matrix deposition, but does not promote tumour angiogenesis or growth of all solid tumours.

THE INFLUENCE OF THE ORIENTATION OF THE COLLAGEN DIPOLES ON SECOND HARMONIC GENERATION (SHG) WITH HIGH NA UNDER CRYSTALLIZED TYPE I COLLAGEN FIBER MODEL

2012 ◽  
Vol 26 (29) ◽  
pp. 1250148
Author(s):  
FEI FEI WANG ◽  
JIAN MEI LIU ◽  
XIAO YUAN DENG
Keyword(s):  
Second Harmonic Generation ◽  
Harmonic Generation ◽  
Collagen Fiber ◽  
Type I Collagen ◽  
Second Harmonic ◽  
Numerical Aperture ◽  
Orientation Angle ◽  
Type I ◽  
Dipole Orientation ◽  
First Time

In this paper, for the first time, we consider theoretically all the potential orientations of dipoles for second harmonic generation (SHG) under crystallized type I collagen fiber. With high numerical aperture ( NA = 14), the effect of dipole orientation angle Φ on the SHG intensity, on the maximum SHG emergence angles (θ max , φ max ) and the action of these dipole sources on the ratio of forward to backward (F/B) SHG have been studied under different cases of fibrils diameter d1 and the QPM order (m, l) in the crystallized collagen fiber, and it is found that the influential patterns of the same Φ on SHG at different fibrils diameter d1 and the QPM order (m, l) are different. The dipoles arrangement is related to the characteristic changes in biological tissue so that our work may provide a helpful theoretical tool for pathological status detecting.

scholarly journals Second Harmonic Generation in 3-D Uniform Arrangement of Type I Collagen on Nonlinear Optics Microscopy

Scanning ◽  
2013 ◽  
Vol 35 (1) ◽  
pp. 12-16 ◽  
Author(s):  
Z. F. Zhuang ◽  
M. F. Zhu ◽  
Z.Y. Guo ◽  
S. H. Liu
Keyword(s):  
Nonlinear Optics ◽  
Second Harmonic Generation ◽  
Harmonic Generation ◽  
Type I Collagen ◽  
Second Harmonic ◽  
Type I

scholarly journals Giantin is required for intracellular N-terminal processing of type I procollagen

2020 ◽  
Author(s):  
Nicola L. Stevenson ◽  
J. M. Bergen Dylan ◽  
Chrissy L. Hammond ◽  
David J. Stephens
Keyword(s):  
Extracellular Matrix ◽  
Type I Collagen ◽  
Fish Analysis ◽  
Type I ◽  
Matrix Assembly ◽  
Matrix Deposition ◽  
Type I Procollagen ◽  
Main Protein ◽  
Extracellular Matrix Deposition ◽  
Craniofacial Defects

AbstractKnockout of the golgin giantin leads to skeletal and craniofacial defects driven by poorly studied changes in glycosylation and extracellular matrix deposition. Here, we sought to determine how giantin impacts the production of healthy bone tissue by focussing on the main protein component of the osteoid, type I collagen. Giantin mutant zebrafish accumulate multiple spontaneous fractures in their caudal fin, suggesting their bones may be more brittle. Inducing new experimental fractures revealed defects in the mineralisation of newly deposited collagen as well as diminished procollagen reporter expression in mutant fish. Analysis of giantin knockout cells expressing a GFP-tagged procollagen showed that procollagen trafficking is independent of giantin. However, our data show that intracellular N-propeptide processing of pro-α1(I) is defective in the absence of giantin. These data demonstrate a conserved role for giantin in collagen biosynthesis and extracellular matrix assembly. Our work also provides evidence of a giantin-dependent pathway for intracellular procollagen processing.

scholarly journals 3D Collagen-Nanocellulose Matrices Model the Tumour Microenvironment of Pancreatic Cancer

2021 ◽  
Vol 3 ◽  
Author(s):  
Rodrigo Curvello ◽  
Verena Kast ◽  
Mohammed H. Abuwarwar ◽  
Anne L. Fletcher ◽  
Gil Garnier ◽  
...  
Keyword(s):  
Type I Collagen ◽  
Three Dimensional ◽  
Tumour Microenvironment ◽  
Ductal Adenocarcinoma ◽  
Type I ◽  
3D Cultures ◽  
Tumour Spheroids ◽  
Cellulose Nanofibres ◽  
Anti Cancer ◽  
The Individual

Three-dimensional (3D) cancer models are invaluable tools designed to study tumour biology and new treatments. Pancreatic ductal adenocarcinoma (PDAC), one of the deadliest types of cancer, has been progressively explored with bioengineered 3D approaches by deconstructing elements of its tumour microenvironment. Here, we investigated the suitability of collagen-nanocellulose hydrogels to mimic the extracellular matrix of PDAC and to promote the formation of tumour spheroids and multicellular 3D cultures with stromal cells. Blending of type I collagen fibrils and cellulose nanofibres formed a matrix of controllable stiffness, which resembled the lower profile of pancreatic tumour tissues. Collagen-nanocellulose hydrogels supported the growth of tumour spheroids and multicellular 3D cultures, with increased metabolic activity and matrix stiffness. To validate our 3D cancer model, we tested the individual and combined effects of the anti-cancer compound triptolide and the chemotherapeutics gemcitabine and paclitaxel, resulting in differential cell responses. Our blended 3D matrices with tuneable mechanical properties consistently maintain the growth of PDAC cells and its cellular microenvironment and allow the screening of anti-cancer treatments.

scholarly journals Abnormal Mucosal Extracellular Matrix Deposition Is Associated with Increased TGF-β Receptor-expressing Mesenchymal Cells in a Mouse Model of Colitis

2003 ◽  
Vol 51 (9) ◽  
pp. 1177-1189 ◽  
Author(s):  
Christine V. Whiting ◽  
John F. Tarlton ◽  
Michael Bailey ◽  
Clare L. Morgan ◽  
Paul W. Bland
Keyword(s):  
Extracellular Matrix ◽  
Basement Membrane ◽  
Mouse Model ◽  
Type Iv Collagen ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Mesenchymal Cells ◽  
Type I ◽  
Matrix Deposition ◽  
Type Iv

Transforming growth factor-β (TGF-β) depresses mucosal inflammation and upregulates extracellular matrix (ECM) deposition. We analyzed TGF-β receptors RI and RII as well as ECM components using the CD4+ T-cell-transplanted SCID mouse model of colitis. The principal change in colitis was an increased proportion of TGF-β RII+ mucosal mesenchymal cells, predominantly α-smooth muscle actin (SMA)+ myofibroblasts, co-expressing vimentin and basement membrane proteins, but not type I collagen. TGF-β RII+ SMA− fibroblasts producing type I collagen were also increased, particularly in areas of infiltration and in ulcers. Type IV collagen and laminin were distributed throughout the gut lamina propria in disease but were restricted to the basement membrane in controls. In areas of severe epithelial damage, type IV collagen was lost and increased type I collagen was observed. To examine ECM production by these cells, mucosal mesenchymal cells were isolated. Cultured cells exhibited a similar phenotype and matrix profile to those of in vivo cells. The data suggested that there were at least two populations of mesenchymal cells responsible for ECM synthesis in the mucosa and that ligation of TGF-β receptors on these cells resulted in the disordered and increased ECM production observed in colitic mucosa.

Influence of Nonenzymatic Glycation in Dentinal Collagen on Dental Caries

2016 ◽  
Vol 95 (13) ◽  
pp. 1528-1534 ◽  
Author(s):  
Y. Matsuda ◽  
J. Miura ◽  
M. Shimizu ◽  
T. Aoki ◽  
M. Kubo ◽  
...  
Keyword(s):  
Western Blotting ◽  
Fluorescence Lifetime ◽  
Type I Collagen ◽  
Second Harmonic ◽  
Collagen Molecule ◽  
Bacterial Invasion ◽  
Type I ◽  
Nonenzymatic Glycation ◽  
Thin Sections ◽  
Diamond Saw

Advanced glycation end-products (AGEs) are generated via nonenzymatic glycation of dentinal collagen, resulting in accumulation of AGEs in dentin tissue. Since accumulated AGEs cause crosslinking between amino acid polypeptides in the collagen molecule and modify mechanical properties of dentinal collagen, the authors assumed that there would be a significant interaction between the generation of AGEs and progression of caries in dentin. To confirm such an interaction, spectroscopic imaging analyses (i.e., nanosecond fluorescence lifetime imaging and second harmonic generation light imaging) were performed in addition to biochemical and electron microscopic analyses in the present study. Seven carious human teeth were fixed in paraformaldehyde and cut longitudinally into 1-mm sections using a low-speed diamond saw for the following analyses. In transmission electron microscopy (TEM) analysis, nondecalcified specimens were embedded in epoxy resin and sliced into thin sections for observation. For the immunohistochemical analysis, the specimens were paraffin embedded after decalcification for 2 wk and sectioned with a microtome. Resultant sections were stained with anti-AGE and anticollagen antibodies. The demineralized specimens were used for spectroscopic analyses without additional treatment. For Western blotting analysis, specimens were separated into carious and sound dentin. Each specimen was homogenized with a bead crusher and an ultrasonic homogenizer and then treated with hydrochloric acid. In carious dentin, the collagen fibers showed an amorphous structure in the TEM image, and the AGEs were localized in the areas of bacterial invasion in the immunostaining image. The total amount of AGEs in carious dentin was higher than in sound dentin in Western blotting. The ultrastructure of type I collagen and total amount of AGEs varied markedly in the dentinal caries region. The fluorescence lifetime was shorter in the carious area than that in the sound areas, indicating an increase of AGEs in the carious area. The increase of AGEs could influence the progression of dentinal caries.

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