scholarly journals The Effect of Glucagon-Like Peptide-2 Receptor Agonists on Colonic Anastomotic Wound Healing

2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Heather A. Redstone ◽  
William D. Buie ◽  
David A. Hart ◽  
Laurie Wallace ◽  
Pamela J. Hornby ◽  
...  
Keyword(s):  
Wound Healing ◽  
Type I Collagen ◽  
Therapeutic Potential ◽  
Bursting Pressure ◽  
Type Iii Collagen ◽  
Type I ◽  
Mrna Levels ◽  
Hypoxic Conditions ◽  
Glucagon Like Peptide ◽  
Anastomotic Strength

Background. Glucagon-like peptide 2 (GLP-2) is an intestinal specific trophic hormone, with therapeutic potential; the effects on intestinal healing are unknown. We used a rat model of colonic healing, under normoxic, and stress (hypoxic) conditions to examine the effect of GLP-2 on intestinal healing.Methods. Following colonic transection and reanastomosis, animals were randomized to one of six groups (n=8/group): controls, native GLP-2, long-acting GLP-2 (GLP-2- MIMETIBODY, GLP-2-MMB), animals were housed under normoxic or hypoxic (11%  O2) conditions. Animals were studied five days post-operation for anastomotic strength and wound characteristics.Results. Anastomotic bursting pressure was unchanged by GLP-2 or GLP-2-MMB in normoxic or hypoxic animals; both treatments increased crypt cell proliferation. Wound IL-1βincreased with GLP-2; IFNγwith GLP-2 and GLP-2-MMB. IL-10 and TGF-βwere decreased; Type I collagen mRNA expression increased in hypoxic animals while Type III collagen was reduced with both GLP-2 agonists. GLP-2 MMB, but not native GLP-2 increased TIMP 1-3 mRNA levels in hypoxia.Conclusions. The effects on CCP, cytokines and wound healing were similar for both GLP-2 agonists under normoxic and hypoxic conditions; anastomotic strength was not affected. This suggests that GLP-2 (or agonists) could be safely used peri-operatively; direct studies will be required.

scholarly journals Collagen synthesis by cultured rabbit aortic smooth-muscle cells. Alteration with phenotype

1990 ◽  
Vol 265 (2) ◽  
pp. 461-469 ◽  
Author(s):  
A H Ang ◽  
G Tachas ◽  
J H Campbell ◽  
J F Bateman ◽  
G R Campbell
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Collagen Synthesis ◽  
Type I Collagen ◽  
Type Iii Collagen ◽  
Type I ◽  
Mrna Levels ◽  
Aortic Smooth Muscle ◽  
Phenotypic State ◽  
Synthetic Phenotype

Enzymically isolated rabbit aortic smooth-muscle cells (SMC) in the first few days of primary culture express a ‘contractile phenotype’, but with time these cells modulate to a ‘synthetic phenotype’. Synthetic-state SMC are able to proliferate, and, provided that they undergo fewer than 5 cumulative population doublings, return to the contractile phenotype after reaching confluency [Campbell, Kocher, Skalli, Gabbiani & Campbell (1989) Arteriosclerosis 9, 633-643]. The present study has determined the synthesis of collagen, at the protein and mRNA levels, by cultured SMC as they undergo a change in phenotypic state. The results show that, upon modulating to the synthetic phenotype, SMC synthesized 25-30 times more collagen than did contractile cells. At the same time, non-collagen-protein synthesis increased only 5-6-fold, indicating a specific stimulation of collagen synthesis. Steady-state mRNA levels are also elevated, with alpha 2(I) and alpha 1(III) mRNA levels 30 times and 20 times higher respectively, probably reflecting increased transcriptional activity. Phenotypic modulation was also associated with an alteration in the relative proportions of type I and III collagens synthesized, contractile SMC synthesizing 78.1 +/- 3.6% (mean +/- S.D.) type I collagen and 17.5 +/- 4.7% type III collagen, and synthetic cells synthesizing 90.3 +/- 2.0% type I collagen and 5.8% +/- 1.8% type III collagen. Enrichment of type I collagen was similarly noted at the mRNA level. On return to the contractile state, at confluency, collagen production and the percentage of type I collagen decreased. This further illustrates the close association between the phenotypic state of SMC and their collagen-biosynthetic phenotype.

scholarly journals Glucagon-Like Peptide-2 Analogue ZP1849 Augments Colonic Anastomotic Wound Healing

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Marie Kjaer ◽  
Wayne Russell ◽  
Peter Schjerling ◽  
Elena Cottarelli ◽  
Kennet N. Christjansen ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Breaking Strength ◽  
Target Area ◽  
Type I ◽  
Mrna Levels ◽  
Protein Levels ◽  
Soluble Collagen ◽  
Cox 2 ◽  
Glucagon Like Peptide

Background. The enteroendocrine hormone glucagon-like peptide- (GLP-) 2 is a potent trophic factor in the gastrointestinal tract. The GLP-2 receptor (GLP-2R) is expressed in the stroma of the large bowel wall, which is the major therapeutic target area to prevent anastomotic leakage. We investigated the efficacy of the long-acting GLP-2 analogue ZP1849 on colonic anastomotic wound healing. Methods. Eighty-seven male Wistar rats were stratified into four groups and received daily treatment with vehicle or ZP1849 starting one day before (day -1) end-to-end anastomosis was constructed in the left colon on day 0, and on days 0 (resected colon segment), 3, and 5, gene expressions of GLP-2R, Ki67, insulin-like growth factor- (IGF-) 1, type I (COL1A1) and type III (COL3A1) procollagens, cyclooxygenase- (COX-) 1, COX-2, and matrix metalloproteinase- (MMP-) 7 were quantified by RT-qPCR. Breaking strength, myeloperoxidase (MPO), transforming growth factor- (TGF-) β1, and soluble collagen proteins were measured on days 3 and 5. Results. ZP1849 treatment increased Ki67 (P<0.0001) and IGF-1 (P<0.05) mRNA levels in noninjured colon day 0, and postoperatively in the anastomotic wounds compared to vehicle-treated rats. ZP1849-treated rats had increased (P=0.042) anastomotic breaking strength at day 5 compared with vehicle. COL1A1 and COL3A1 mRNA levels (P<0.0001) and soluble collagen proteins (P<0.05) increased from day 3 to day 5 in ZP1849-treated rats, but not in vehicle-treated rats. COX-2 mRNA and MPO protein levels decreased from day 3 to day 5 (P<0.001) in both groups. ZP1849 treatment reduced TGF-β1 protein levels on day 5 (P<0.001) but did not impact MMP-7 transcription. Conclusions. The GLP-2 analogue ZP1849 increased breaking strength, IGF-1 expression, and cell proliferation, which may be beneficial for colonic anastomotic wound healing.

scholarly journals Potential therapeutic effect of thymoquinone and/or bee pollen on fluvastatin-induced hepatitis in rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Amro E. Mohamed ◽  
Mohammed A. El-Magd ◽  
Karim S. El-Said ◽  
Mohamed El-Sharnouby ◽  
Ehab M. Tousson ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Therapeutic Potential ◽  
Combined Therapy ◽  
Individual Treatment ◽  
Type I ◽  
Mrna Levels ◽  
Gamma Glutamyl Transpeptidase ◽  
Bee Pollen

AbstractHepatitis is one of earlier, but serious, signs of liver damage. High doses of statins for a long time can induce hepatitis. This study aimed to evaluate and compare the therapeutic potential of thymoquinone (TQ) and bee pollen (BP) on fluvastatin (F)-induced hepatitis in rats. Rats were randomly divided into: group 1 (G1, control), G2 (F, hepatitis), G3 (F + TQ), G4 (F + BP), and G5 (F + TQ + BP). Single treatment with TQ or BP relieved fluvastatin-induced hepatitis, with best effect for the combined therapy. TQ and/or BP treatment significantly (1) reduced serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transpeptidase, and total bilirubin, (2) decreased malondialdehyde levels and increased level of reduced glutathione, and activities of glutathione peroxidase and catalase in the liver, (3) improved liver histology with mild deposition of type I collagen, (4) increased mRNA levels of transforming growth factor beta 1, nuclear factor Kappa B, and cyclooxygenase 1 and 2, and (5) decreased tumor necrosis factor alpha and upregulated interleukin 10 protein in the liver. These data clearly highlight the ability of TQ and BP combined therapy to cause better ameliorative effects on fluvastatin-induced hepatitis than individual treatment by each alone.

Chitosan-microencapsulated rhEGF in promoting wound healing

2021 ◽  
Vol 30 (Sup9a) ◽  
pp. IXi-IXxi
Author(s):  
Hsin-Chung Tsai ◽  
Christine Sheng ◽  
Le-Shin Chang ◽  
Zhi-Hong Wen ◽  
Ching-Yin Ho ◽  
...  
Keyword(s):  
Wound Healing ◽  
Type I Collagen ◽  
Normal Skin ◽  
Hair Follicles ◽  
Type Iii Collagen ◽  
Type I ◽  
Treatment Groups ◽  
Spray Solution ◽  
Significant Difference ◽  
Spray Treatment

Aims: Chitosan and epidermal growth factor (EGF) have been shown to improve wound healing. This study investigates the healing effects of a spray solution (NewEpi, JoyCom Bio-Chem Co. Ltd., Taiwan) containing recombinant human EGF (rhEGF) delivered via a newly patented technology—chitosan microencapsulated nanoparticles. Methods: On Wistar rats, two full-thickness wounds on the dorsum bilateral of the spine were created. The rats were randomised to the following treatment groups: hydrogel, wet dressing, foam, rhEGF spray and rhEGF spray+foam. Sterile dressings were applied and changed daily. A total of 2μg of rhEGF was administered in two sprays during each dressing change. All animals were euthanised on day 14. Tissue samples were taken from the wound bed, including an area of 2cm surrounding the wound margin for histological evaluations. Results: Wounds treated with the rhEGF spray achieved the greatest size reduction by day 14 compared with other types of conventional dressings. An overall significant difference in levels of collagen synthesis existed between groups (p<0.01). Pair-wise comparisons showed that the rhEGF spray treatment significantly promoted higher levels of mature Type I collagen than any other conventional dressings (p<0.01), whereas non-rhEGF treatments resulted in higher levels of Type III collagen. The regenerated tissue in rhEGF spray treatment groups was also in alignment with that of normal skin. Epidermis, dermis and hair follicles were easily observed in wounds treated with the rhEGF spray. Conclusion: The major challenge of topical application of rhEGF was overcome by using a new drug delivery technology: chitosan–rhEGF nanoparticles. The positive healing effects observed in this study suggest the therapeutic potentials of this novel rhEGF topical spray solution.

scholarly journals Heat delays skin wound healing in mice

2016 ◽  
Vol 242 (3) ◽  
pp. 258-266 ◽  
Author(s):  
Marco Aurélio dos Santos-Silva ◽  
Eduardo Tavares Lima Trajano ◽  
Fernanda Seabra Schanuel ◽  
Andréa Monte-Alto-Costa
Keyword(s):  
Wound Healing ◽  
Protein Expression ◽  
Visible Light ◽  
Type I Collagen ◽  
In Vivo Studies ◽  
Type Iii Collagen ◽  
Type I ◽  
Skin Wound Healing ◽  
Thermal Chamber

In vivo studies have shown that the combination of infrared radiation (IR) and visible light (VIS) is responsible for the activation of metaloproteinases, causing matrix degradation and damage to healthy skin. However, the role of heat originating from the VIS spectrum on wound healing remains poorly understood. Our objective was to investigate the macroscopic, microscopic and biochemical effects of heat induced by visible light on cutaneous wound healing in mice. Male mice were anesthetized, subjected to a cutaneous excisional wound and divided into two groups ( n = 10/group) exposed to 23℃ or 43℃ in a thermal chamber for 30 min every other day, for 13 days. On day 14, the animals were sacrificed, and their lesions were processed for histochemistry, immunohistochemistry and protein expression analysis. The wound area was 42% greater 11 days ( p < 0.01) and 29% greater 14 days ( p < 0.001) after wounding in the 43℃ group than in the 23℃ group. The 43℃ group presented a lower (17%) percentage of reepithelialized wounds ( p < 0.001) 14 days after wounding. The length of the epidermal gap was greater in the 43℃ group ( p < 0.01). The volume density of myofibroblasts and the number of F4/80-positive macrophages was greater in the 43℃ group ( p < 0.05). The 43℃ group showed increased protein expression of type III collagen ( p < 0.001), decreased protein expression of type I collagen ( p < 0.05), increased MMP-1 expression ( p < 0.05), and decreased MMP-2 activity ( p < 0.001). The protein expression of fibrillin-1 ( p < 0.001), MMP-12 ( p < 0.05), TGF-β 1/2/3 ( p < 0.01) and ERK activation ( p < 0.05) was increased in the 43℃ group. Our results suggest that heat delays the stages of wound healing in mice.

scholarly journals Effects of chitosan-collagen dressing on wound healing in vitro and in vivo assays

2021 ◽  
Vol 19 ◽  
pp. 228080002198969
Author(s):  
Min-Xia Zhang ◽  
Wan-Yi Zhao ◽  
Qing-Qing Fang ◽  
Xiao-Feng Wang ◽  
Chun-Ye Chen ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Dressing ◽  
Type I Collagen ◽  
Inhibition Zone ◽  
Negative Control ◽  
Type I ◽  
Nih3t3 Cells ◽  
Post Operation

The present study was designed to fabricate a new chitosan-collagen sponge (CCS) for potential wound dressing applications. CCS was fabricated by a 3.0% chitosan mixture with a 1.0% type I collagen (7:3(w/w)) through freeze-drying. Then the dressing was prepared to evaluate its properties through a series of tests. The new-made dressing demonstrated its safety toward NIH3T3 cells. Furthermore, the CCS showed the significant surround inhibition zone than empty controls inoculated by E. coli and S. aureus. Moreover, the moisture rates of CCS were increased more rapidly than the collagen and blank sponge groups. The results revealed that the CCS had the characteristics of nontoxicity, biocompatibility, good antibacterial activity, and water retention. We used a full-thickness excisional wound healing model to evaluate the in vivo efficacy of the new dressing. The results showed remarkable healing at 14th day post-operation compared with injuries treated with collagen only as a negative control in addition to chitosan only. Our results suggest that the chitosan-collagen wound dressing were identified as a new promising candidate for further wound application.

Abstract 14664: Reduced Activin Like Kinase 1 Activity Promotes Cardiac Fibrosis in Heart Failure

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Kevin Morine ◽  
Vikram Paruchuri ◽  
Xiaoying Qiao ◽  
Emily Mackey ◽  
Mark Aronovitz ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Remodeling ◽  
Cardiac Fibrosis ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Left Ventricular ◽  
Lv Function ◽  
Type I ◽  
Mrna Levels ◽  
Protein Levels

Introduction: Activin receptor like kinase 1 (ALK1) mediates signaling via transforming growth factor beta-1 (TGFb1), a pro-fibrogenic cytokine. No studies have defined a role for ALK1 in heart failure. We tested the hypothesis that reduced ALK1 expression promotes maladaptive cardiac remodeling in heart failure. Methods and Results: ALK1 mRNA expression was quantified by RT-PCR in left ventricular (LV) tissue from patients with end-stage heart failure and compared to control LV tissue obtained from the National Disease Research Interchange (n=8/group). Compared to controls, LV ALK1 mRNA levels were reduced by 85% in patients with heart failure. Next, using an siRNA approach, we tested whether reduced ALK1 levels promote TGFb1-mediated collagen production in human cardiac fibroblasts. Treatment with an ALK1 siRNA reduced ALK1 mRNA levels by 75%. Compared to control, TGFb1-mediated Type I collagen and pSmad-3 protein levels were 2.5-fold and 1.7-fold higher, respectively, after ALK1 depletion. To explore a role for ALK1 in heart failure, ALK1 haploinsufficient (ALK1) and wild-type mice (WT; n=8/group) were studied 2 weeks after thoracic aortic constriction (TAC). Compared to WT, baseline LV ALK1 mRNA levels were 50% lower in ALK1 mice. Both LV and lung weights were higher in ALK1 mice after TAC. Cardiomyocyte area and LV mRNA levels of BNP, RCAN, and b-MHC were increased similarly, while SERCa levels were reduced in both ALK1 and WT mice after TAC. Compared to WT, LV fibrosis (Figure) and Type 1 Collagen mRNA and protein levels were higher among ALK1 mice. Compared to WT, LV fractional shortening (48±12 vs 26±10%, p=0.01) and survival (Figure) were lower in ALK1 mice after TAC. Conclusions: Reduced LV expression of ALK1 is associated with advanced heart failure in humans and promotes early mortality, impaired LV function, and cardiac fibrosis in a murine model of heart failure. Further studies examining the role of ALK1 and ALK1 inhibitors on cardiac remodeling are required.

Change in phenotype in long-term cultures of a clonal rat bone cell line: switch to the synthesis of α1 (I)-trimer collagen

1984 ◽  
Vol 62 (6) ◽  
pp. 462-469 ◽  
Author(s):  
Hardy Limeback ◽  
Kichibee Otsuka ◽  
Kam-Ling Yao ◽  
Jane E. Aubin ◽  
Jaro Sodek
Keyword(s):  
Collagen Synthesis ◽  
Type I Collagen ◽  
Bone Cell ◽  
Detectable Effect ◽  
Prostaglandin E ◽  
Intracellular Camp ◽  
Type Iii Collagen ◽  
Type I ◽  
Type Iii ◽  
Type V

A number of bone cell clones isolated from rat calvaria have been maintained in culture for more than 3 years. Several of these clones have undergone dramatic changes in phenotype. One of these clones, RGB 2.2, was observed originally to have a fibroblastic morphology in culture and to respond to parathyroid hormone (PTH), but not prostaglandin E2 (PGE2), with an increase in intracellular cAMP. Throughout several passages in early subcultures, these cells synthesized mostly type I collagen, with small amounts of type III and type V collagens. Whereas PTH had no detectable effect on collagen synthesis, PGE2 decreased the amount of total cell layer collagen, with the greatest effect on type III collagen, while increasing the proportion of type V collagen. Subsequent studies on these cells during 3 years in culture have indicated changes in their phenotype including a progressive change in morphology to a more cuboidal shape and a change in collagen synthesis, the cells producing large amounts of the "embryonic" collagen, α1(I) trimer. The reason(s) for the change in collagen expression is unknown, but may be the result of a change in which gene(s) is being expressed.

scholarly journals PERITONEAL ADHESIONS TYPE I, III AND TOTAL COLLAGEN ON POLYPROPYLENE AND COATED POLYPROPYLENE MESHES: EXPERIMENTAL STUDY IN RATS

2017 ◽  
Vol 30 (2) ◽  
pp. 77-82 ◽  
Author(s):  
Lucas Félix ROSSI ◽  
Manoel Roberto Maciel TRINDADE ◽  
Armando José D`ACAMPORA ◽  
Luise MEURER
Keyword(s):  
Type I Collagen ◽  
Cell Types ◽  
Type Iii Collagen ◽  
Type I ◽  
Abdominal Adhesions ◽  
Peritoneal Adhesions ◽  
Type Iii ◽  
Total Collagen

ABSTRACT Background: Hernia correction is a routinely performed treatment in surgical practice. The improvement of the operative technique and available materials certainly has been a great benefit to the quality of surgical results. The insertion of prostheses for hernia correction is well-founded in the literature, and has become the standard of treatment when this type of disease is discussed. Aim: To evaluate two available prostheses: the polypropylene and polypropylene coated ones in an experimental model. Methods: Seven prostheses of each kind were inserted into Wistar rats (Ratus norvegicus albinus) in the anterior abdominal wall of the animal in direct contact with the viscera. After 90 days follow-up were analyzed the intra-abdominal adhesions, and also performed immunohistochemical evaluation and videomorphometry of the total, type I and type III collagen. Histological analysis was also performed with hematoxylin-eosin to evaluate cell types present in each mesh. Results: At 90 days the adhesions were not different among the groups (p=0.335). Total collagen likewise was not statistically different (p=0.810). Statistically there was more type III collagen in the coated polypropylene group (p=0.039) while type I was not different among the prostheses (p=0.050). The lymphocytes were statistically more present in the polypropylene group (p=0.041). Conclusion: The coated prosthesis was not different from the polypropylene one regarding the adhesion. Total and type I collagen were not different among the groups, while type III collagen was more present on the coated mesh. There was a greater number of lymphocytes on the polypropylene mesh.

Sign in / Sign up

Export Citation Format

Share Document