scholarly journals Change in Long-Spacing Collagen in Descemet's Membrane of Diabetic Goto-Kakizaki Rats and Its Suppression by Antidiabetic Agents

2008 ◽  
Vol 2008 ◽  
pp. 1-8 ◽  
Author(s):  
Yoshihiro Akimoto ◽  
Hajime Sawada ◽  
Mica Ohara-Imaizumi ◽  
Shinya Nagamatsu ◽  
Hayato Kawakami
Keyword(s):  
Wistar Rats ◽  
Collagen Type I ◽  
Diabetic Rats ◽  
Type I ◽  
Antidiabetic Agents ◽  
Gk Rats ◽  
Extracellular Matrix Components ◽  
Descemet's Membrane ◽  
Age Dependent ◽  
Descemet’S Membrane

We examined changes in the ultrastructure and localization of major extracellular matrix components, including 5 types of collagen (type I, III, IV, VI, and VIII), laminin, fibronectin, and heparan sulfate proteoglycan in Descemet's membrane of the cornea of diabetic GK rats. In the cornea of diabetic GK rats, more long-spacing collagen fibrils were observed in Descemet's membrane than in the membrane of the nondiabetic Wistar rats. Both GK and Wistar rats showed an age-dependent increase in the density of the long-spacing collagen. Immunoelectron microscopy showed that type VIII collagen was localized in the internodal region of the long-spacing collagen, which was not labelled by any of the other antibodies used. The antidiabetic agents nateglinide and glibenclamide significantly suppressed the formation of the long-spacing collagen in the diabetic rats. Long-spacing collagen would thus be a useful indicator for studying diabetic changes in the cornea and the effect of antidiabetic agents.

scholarly journals Antifibrotic cardioprotection of berberine via downregulating myocardial IGF-1 receptor-regulated MMP-2/MMP-9 expression in diabetic rats

2018 ◽  
Vol 315 (4) ◽  
pp. H802-H813 ◽  
Author(s):  
Guohua Li ◽  
Wenjuan Xing ◽  
Min Zhang ◽  
Fenghao Geng ◽  
Hongyan Yang ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
High Glucose ◽  
Cardiac Fibrosis ◽  
Collagen Type ◽  
Cardiac Fibroblasts ◽  
Collagen Type I ◽  
Diabetic Rats ◽  
Type I ◽  
Antifibrotic Effect

Diabetic cardiac fibrosis increases ventricular stiffness and facilitates the occurrence of diastolic dysfunction. Our previous studies have shown that berberine, a natural alkaloid, attenuates cardiac ischemia-reperfusion injury in diabetic rats. The aim of present study was to investigate the effects of long-term berberine treatment on cardiac remodeling in diabetic rats and the underlying mechanisms. Diabetic rats induced by low-dose streptozotocin injection combined with 8 wk of high-fat diet displayed significant cardiac matrix collagen deposition and dysfunction, whereas berberine administration (200 mg·kg−1·day−1, gavage 4 wk) significantly ameliorated cardiac fibrosis and dysfunction and reduced cardiac IGF-1 receptor (IGF-1R) expression in diabetic rats. Interestingly, IGF-1R expression was upregulated in cardiac fibroblasts isolated from diabetic hearts or cultured in high-glucose conditions (30 mM). High glucose treatment or IGF-1R overexpression increased matrix metalloproteinase (MMP)-2/MMP-9 expression, α-smooth muscle actin (α-SMA), and collagen type I expression in cardiac fibroblasts. In contrast, berberine treatment significantly inhibited IGF-1R expression and exerted an antifibrotic effect in high glucose-cultured cardiac fibroblasts, as manifested by decreased MMP-2/MMP-9, α-SMA, and collagen type I expression, whereas IGF-1R siRNA plus berberine treatment did not further enhance this antifibrotic effect compared with berberine treatment alone. Taken together, long-term berberine treatment ameliorates cardiac fibrosis and dysfunction by downregulating IGF-1R expression in cardiac fibroblasts and subsequently reducing MMP-2/MMP-9, α-SMA, and collagen type I expression in diabetic hearts. The findings suggest the therapeutic potential of berberine for diabetic cardiomyopathy associated with cardiac fibrosis. NEW & NOTEWORTHY Berberine downregulated IGF-1 receptor expression and matrix metalloproteinase-2/matrix metalloproteinase-9 levels in cardiac fibroblasts and thus inhibited fibroblast differentiation and collagen overproduction in diabetic hearts, suggesting a novel mechanism for antifibrotic cardioprotection of berberine in type 2 diabetes.

Arginase inhibition restores in vivo coronary microvascular function in type 2 diabetic rats

2011 ◽  
Vol 300 (4) ◽  
pp. H1174-H1181 ◽  
Author(s):  
Julia Grönros ◽  
Christian Jung ◽  
Jon O. Lundberg ◽  
Ruha Cerrato ◽  
Claes-Göran Östenson ◽  
...  
Keyword(s):  
Vascular Function ◽  
Wistar Rats ◽  
Diabetic Rats ◽  
Microvascular Function ◽  
Vascular Integrity ◽  
Gk Rats ◽  
Type 2 Diabetic ◽  
Coronary Microvascular Function

Nitric oxide (NO) is crucial for maintaining normal endothelial function and vascular integrity. Increased arginase activity in diabetes might compete with NO synthase (NOS) for their common substrate arginine, resulting in diminished production of NO. The aim of this study was to evaluate coronary microvascular function in type 2 diabetic Goto-Kakizaki (GK) rats using in vivo coronary flow velocity reserve (CFVR) and the effect of arginase inhibition to restore vascular function. Different groups of GK and Wistar rats were given vehicle, the arginase inhibitor Nω-hydroxy-nor-l-arginine (nor-NOHA), l-arginine, and the NOS inhibitor NG-monomethyl -l-arginine (l-NMMA). GK rats had impaired CFVR compared with Wistar rats (1.31 ± 0.09 vs. 1.87 ± 0.05, P < 0.001). CFVR was restored by nor-NOHA treatment compared with vehicle in GK rats (1.71 ± 0.13 vs. 1.23 ± 0.12, P < 0.05) but remained unchanged in Wistar rats (1.88 ± 0.10 vs. 1.79 ± 0.16). The beneficial effect of nor-NOHA in GK rats was abolished after NOS inhibition. CFVR was not affected by arginine compared with vehicle. Arginase II expression was increased in the aorta and myocardium from GK rats compared with Wistar rats. Citrulline-to-ornithine and citrulline-to-arginine ratios measured in plasma increased significantly more in GK rats than in Wistar rats after nor-NOHA treatment, suggesting a shift of arginine utilization from arginase to NOS. In conclusion, coronary artery microvascular function is impaired in the type 2 diabetic GK rat. Treatment with nor-NOHA restores the microvascular function by a mechanism related to increased utilization of arginine by NOS and increased NO availability.

scholarly journals Morphometric analysis of the human endoneurial extracellular matrix components during aging

2021 ◽  
Vol 73 (1) ◽  
pp. 103-110
Author(s):  
Braca Kundalic ◽  
Sladjana Ugrenovic ◽  
Ivan Jovanovic ◽  
Vladimir Petrovic ◽  
Aleksandar Petrovic ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Collagen Type ◽  
Linear Regression Analysis ◽  
Collagen Type I ◽  
Nerve Fibers ◽  
Collagen Type Iv ◽  
Type I ◽  
Type Iv ◽  
Ecm Proteins ◽  
Extracellular Matrix Components

The aim of this study was to analyze the expression of extracellular matrix (ECM) proteins in human endoneurium during aging. We harvested 15 cadaveric sural nerves, distributed in 3 age groups (I: 25-44, II: 45-64, III: 65-86 years old). Histological sections were stained immunohistochemically for the presence of collagen type I, type IV and laminin, and the ImageJ processing program was used in morphometrical analysis to determine the percentages of these endoneurial proteins. In two younger groups, the endoneurial matrix of the sural nerve was composed from about equal proportions of these proteins, which may be considered a favorable microenvironment for the regeneration of nerve fibers. Linear regression analysis showed a significant increase in endoneurial collagen type IV with age, while collagen type I and laminin significantly decreased during the aging process. In cases older than 65 years, remodeling of the endoneurial matrix was observed to be significantly higher for the presence of collagen type IV, and lower for the expression of collagen type I and laminin. This age-related imbalance of ECM proteins could represent a disadvantageous microenvironment for nerve fiber regeneration in older adults. Our findings contribute to the development of therapeutic approaches for peripheral nerve regeneration.

C6 Mediates Chronic Progression of Tubulointerstitial Damage in Rats with Remnant Kidneys

2002 ◽  
Vol 13 (4) ◽  
pp. 928-936 ◽  
Author(s):  
Masaomi Nangaku ◽  
Jeffrey Pippin ◽  
William G. Couser
Keyword(s):  
Renal Function ◽  
Renal Disease ◽  
Type I Collagen ◽  
Collagen Type ◽  
Interstitial Fibrosis ◽  
Collagen Type I ◽  
Collagen Type Iv ◽  
Type I ◽  
Tubulointerstitial Injury ◽  
Extracellular Matrix Components

ABSTRACT. Although it was once considered only a marker of glomerular damage, accumulating evidence indicates that proteinuriaper seis nephrotoxic and contributes to the progression of renal injury. Several studies have demonstrated that activation of complement in proteinuric urine results in tubular and interstitial damage. It was previously demonstrated that acute complement-mediated interstitial disease is induced by C5b-9. Here the role of C5b-9 in the progression of chronic proteinuric renal disease was investigated in a nonimmunologic remnant kidney model. Five-sixths nephrectomies were performed for normocomplementemic control and C6-deficient PVG rats. Tubulointerstitial injury was assessed by measurement of two independent markers of tubular injury (i.e., vimentin and osteopontin), interstitial accumulation of the extracellular matrix components collagen type I, collagen type IV, and laminin, interstitial macrophage infiltration, and renal function. The two groups developed similar levels of proteinuria and BP. Whereas C3 deposition on the brush border was equivalent for rats in the two groups, C5b-9 deposition was observed only for normocomplementemic rats. At day 35, the degrees of both tubulointerstitial injury and renal failure were the same for the two groups. Tubulointerstitial injury in normocomplementemic rats was still severe at day 70. In contrast, interstitial injury in C6-deficient rats had improved markedly at day 70, with improvements in renal function. In a rat model of chronic progressive renal disease secondary to nephron loss, the initial interstitial changes are complement-independent and largely reversible, whereas progressive interstitial fibrosis is mediated predominantly by C5b-9. Treatment to reduce C5b-9 attack in tubular cells may slow progression and facilitate recovery.

Effects of Type II diabetes on capillary hemodynamics in skeletal muscle

2006 ◽  
Vol 291 (5) ◽  
pp. H2439-H2444 ◽  
Author(s):  
Danielle J. Padilla ◽  
Paul McDonough ◽  
Brad J. Behnke ◽  
Yutaka Kano ◽  
K. Sue Hageman ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Glucose ◽  
Type Ii Diabetes ◽  
Capillary Tube ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Diabetic Patients ◽  
Type I ◽  
Type Ii ◽  
Gk Rats

Microcirculatory red blood cell (RBC) hemodynamics are impaired within skeletal muscle of Type I diabetic rats (Kindig CA, Sexton WL, Fedde MR, and Poole DC. Respir Physiol 111: 163–175, 1998). Whether muscle microcirculatory dysfunction occurs in Type II diabetes, the more prevalent form of the disease, is unknown. We hypothesized that Type II diabetes would reduce the proportion of capillaries supporting continuous RBC flow and RBC hemodynamics within the spinotrapezius muscle of the Goto-Kakizaki Type II diabetic rat (GK). With the use of intravital microscopy, muscle capillary diameter ( dc), capillary lineal density, capillary tube hematocrit (Hctcap), RBC flux ( FRBC), and velocity ( VRBC) were measured in healthy male Wistar (control: n = 5, blood glucose, 105 ± 5 mg/dl) and male GK ( n = 7, blood glucose, 263 ± 34 mg/dl) rats under resting conditions. Mean arterial pressure did not differ between groups ( P > 0.05). Sarcomere length was set to a physiological length (∼2.7 μm) to ensure that muscle stretching did not alter capillary hemodynamics; dc was not different between control and GK rats ( P > 0.05), but the percentage of RBC-perfused capillaries (control: 93 ± 3; GK: 66 ± 5 %), Hctcap, VRBC, FRBC, and O2 delivery per unit of muscle were all decreased in GK rats ( P < 0.05). This study indicates that Type II diabetes reduces both convective O2 delivery and diffusive O2 transport properties within muscle microcirculation. If these microcirculatory deficits are present during exercise, it may provide a basis for the reduced O2 exchange characteristic of Type II diabetic patients.

scholarly journals Effectiveness of gold sea cucumber (Stichopus hermanii) extracts in accelerating the healing process of oral traumatic ulcer in rats

2019 ◽  
Vol 31 (3) ◽  
pp. 208
Author(s):  
Dian Widya Damaiyanti ◽  
Pratiwi Soesilowati ◽  
Ira Arundina ◽  
Rima Parwati Sari
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Wistar Rats ◽  
Sea Cucumber ◽  
Collagen Type ◽  
Pearson Correlation ◽  
Healing Process ◽  
Body Weight Loss ◽  
Collagen Type I ◽  
Type I

Introduction: Gold sea cucumber (Stichopus hermanii) is a marine organism that contains omega-3 and glycosaminoglycan for enhancing collagen needed in the healing process. This study was aimed to determine the effectiveness of gold sea cucumber extracts in accelerating the healing process of oral traumatic ulcer in Wistar rats, in terms of the correlation between collagen type I expression, ulcer diameter, and body weight loss. Methods: Twenty Wistar rats (Rattus norvegicus) was divided into four groups and treated with gold sea cucumber extracts with the concentration of 80%, 40%, and 20% in the form of 0.1 ml gel daily. The negative control group received no treatment. Ulceration of the lower lip of labial mucosa was induced by a burnisher. The animals were observed for 7 days, during which they were weighed and the ulcers diameter was measured. The rats were then sacrificed after 7 days of treatment. Histometric analysis of collagen type I expression was also performed. Data obtained were analysed for differences between the group with one-way ANOVA test and the correlation was analysed with the Pearson test. Results: The significant differences (p < 0.05) between treatment groups was found in the ulcer diameters and the collagen type I expression. The most decreased ulcer diameter and the highest collagen type I expression detected in the group of treatment with a concentration of 80% — no significant differences found in the weight loss between-groups (p > 0.05). Strong correlation was also found between the expression of collagen type I and diameter of ulcer (Pearson correlation = 0.599, p = 0.05), however, no correlation found between weight loss with the expression of collagen type I (Pearson correlation = -0.102, p = 0.66), and the ulcer diameter (Pearson correlation = 0.022, p = 0.92). Conclusion: Gold sea cucumber had a potential benefit to be used as a traumatic ulcer healing medicament. Water extract of gold sea cucumber able to accelerate traumatic ulcer healing by enhancing the production of collagen type I and reduce the diameter of ulcer. There is a strong correlation between collagen type 1 expression and diameter of ulcer, and a weak correlation found between body weight loss and collagen type I expression, also with reducing ulcer diameter.Keywords: Gold sea cucumber, Stichopus hermanii, healing process, traumatic ulcer.

scholarly journals Influence of Collagen and Chondroitin Sulfate (CS) Coatings on Poly-(Lactide-co-Glycolide) (PLGA) on MG 63 Osteoblast-Like Cells

2011 ◽  
pp. 797-813 ◽  
Author(s):  
M. VANDROVCOVÁ ◽  
T. DOUGLAS ◽  
D. HAUK ◽  
B. GRÖSSNER-SCHREIBER ◽  
J. WILTFANG ◽  
...  
Keyword(s):  
Chondroitin Sulfate ◽  
Collagen Type I ◽  
Cell Number ◽  
Collagen I ◽  
Osteoblastic Cell ◽  
Type I ◽  
Bone Contact ◽  
Osteoblastic Cell Line ◽  
Collagen Coating ◽  
Extracellular Matrix Components

Poly-(lactide-co-glycolide) (PLGA) is an FDA-approved biodegradable polymer which has been widely used as a scaffold for tissue engineering applications. Collagen has been used as a coating material for bone contact materials, but relatively little interest has focused on biomimetic coating of PLGA with extracellular matrix components such as collagen and the glycosaminoglycan chondroitin sulfate (CS). In this study, PLGA films were coated with collagen type I or collagen I with CS (collagen I/CS) to investigate the effect of CS on the behaviour of the osteoblastic cell line MG 63. Collagen I/CS coatings promoted a significant increase in cell number after 3 days (in comparison to PLGA) and after 7 days (in comparison to PLGA and collagen-coated PLGA). No influence of collagen I or collagen I/CS coatings on the spreading area after 1 day of culture was observed. However, the cells on collagen I/CS formed numerous filopodia and displayed well developed vinculin-containing focal adhesion plaques. Moreover, these cells contained a significantly higher concentration of osteocalcin, measured per mg of protein, than the cells on the pure collagen coating. Thus, it can be concluded that collagen I/CS coatings promote MG 63 cell proliferation, improve cell adhesion and enhance osteogenic cell differentiation.

Diet-induced obesity enhances postprandial glucagon-like peptide-1 secretion in Wistar rats, but not in diabetic Goto-Kakizaki rats

2020 ◽  
pp. 1-13
Author(s):  
Jukkrapong Pinyo ◽  
Hiroshi Hara ◽  
Tohru Hira
Keyword(s):  
Wistar Rats ◽  
Control Diet ◽  
Postprandial Glucose ◽  
Diabetic Rats ◽  
Gk Rats ◽  
Obesity And Diabetes ◽  
Male Wistar Rats ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Insulin Responses

Abstract Glucagon-like peptide-1 (GLP-1) is postprandially secreted from enteroendocrine L-cells and enhances insulin secretion. Currently, it is still controversial whether postprandial GLP-1 responses are altered in obesity and diabetes. To address the issue and to find out possible factors related, we compared postprandial GLP-1 responses in normal rats and in diabetic rats chronically fed an obesogenic diet. Male Wistar rats and diabetic Goto-Kakizaki (GK) rats were fed either a control diet or a high-fat/high-sucrose (HFS, 30 % fat and 40 % sucrose) diet for 26 weeks. Meal tolerance tests were performed for monitoring postprandial responses after a liquid diet administration (62·76 kJ/kg body weight) every 4 or 8 weeks. Postprandial glucose, GLP-1 and insulin responses in Wistar rats fed the HFS diet (WH) were higher than Wistar rats fed the control diet (WC). Although GK rats fed the HFS diet (GH) had higher glycaemic responses than GK rats fed the control diet (GC), these groups had similar postprandial GLP-1 and insulin responses throughout the study. Jejunal and ileal GLP-1 contents were increased by the HFS diet only in Wistar rats. Furthermore, mRNA expression levels of fatty acid receptors (Ffar1) in the jejunum were mildly (P = 0·053) increased by the HFS diet in Wistar rats, but not in GK rats. These results demonstrate that postprandial GLP-1 responses are enhanced under an obesogenic status in normal rats, but not in diabetic rats. Failure of adaptive enhancement of GLP-1 response in GK rats could be partly responsible for the development of glucose intolerance.

scholarly journals rAAV9‐mediated supplementation of miR-29b improve angiotensin-II induced renal fibrosis in mice

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Ju-hong Zhang ◽  
Jing Li ◽  
Yang Ye ◽  
Wang-qi Yu
Keyword(s):  
Renal Injury ◽  
Renal Fibrosis ◽  
Quantitative Polymerase Chain Reaction ◽  
Kidney Tissue ◽  
Critical Factor ◽  
Collagen Type I ◽  
Tubulointerstitial Fibrosis ◽  
Type I ◽  
Extracellular Matrix Components

Abstract Background Renin–angiotensin–aldosterone system activation is the critical factor in renal remodeling and dysfunction. Our previous study suggested that miR-29b may attenuate AngII-induced renal intestinal fibrosis in vitro. In the present study, we aimed to determine whether recombinant rAAV9-mediated miR-29b delivery protects against AngII-induced renal fibrosis and dysfunction. Method Mice were treated with AngII via osmotic mini-pumps, or phosphate-buffered saline. rAAV9 vectors were produced using the rBac-based system in SF9 cells. rAAV9-miR-29b or rAAV9-control-miR was injected into the kidneys of mice subjected to the model of AngII infusion. The role of miR-29b in renal fibrosis was assessed using quantitative polymerase chain reaction, western blot, and histology. Results In AngII-induced fibrotic kidney tissue, miR-29b expression was downregulated. rAAV9-miR-29b delivery significantly reversed renal injury as indicated by decreased serum creatinine and injury related gene expression in AngII-infused mice. Regarding organ remodeling, tubulointerstitial fibrosis and deposition of extracellular matrix components such as collagen type I and type III were significantly decreased in renal tissue from mice delivered rAAV9-miR-29b. Conclusion Our results demonstrate great potential for use of rAAV9 as an applicable vector for delivery of miR-29b as an antifibrogenic factor for treatment of tubulointerstitial fibrosis-induced renal injury.

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