Angiopoietin-1 gene transfer improves impaired wound healing in genetically diabetic mice without increasing VEGF expression

2008 ◽  
Vol 114 (12) ◽  
pp. 707-718 ◽  
Author(s):  
Alessandra Bitto ◽  
Letteria Minutoli ◽  
Maria Rosaria Galeano ◽  
Domenica Altavilla ◽  
Francesca Polito ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Protein Expression ◽  
Wound Repair ◽  
Breaking Strength ◽  
Healing Process ◽  
Diabetic Mice ◽  
Impaired Wound Healing ◽  
Mrna And Protein Expression ◽  
Genetically Diabetic Mice ◽  
Angiopoietin 1

Ang-1 (angiopoietin-1) improves the ineffective angiogenesis and impaired wound healing in diabetes; however, the mechanism underlying this positive effect is still far from being completely understood. In the present study, we investigated whether rAAV (recombinant adeno-associated virus)–Ang-1 gene transfer could improve wound repair in genetically diabetic mice (db+/db+) and the mechanism(s) by which it causes new vessel formation. An incisional skin-wound model in diabetic and normoglycaemic mice was used. After the incision, animals received rAAV–LacZ or rAAV–Ang-1 in the wound edge. After 7 and 14 days, wounds were used to (i) confirm Ang-1 gene transfer, (ii) assess histologically the healing process, (iii) evaluate wound-breaking strength, and (iv) study new vessel formation by PECAM-1 (platelet/endothelial cell adhesion molecule-1) immunostaining. Finally, we investigated VEGF (vascular endothelial growth factor) mRNA and protein levels, eNOS (endothelial NO synthase) expression and VEGFR-1 and VEGFR-2 (VEGF receptor-1 and -2 respectively) immunostaining. The efficiency of Ang-1 gene transfer was confirmed by increased mRNA and protein expression of the protein. rAAV–Ang-1 significantly improved the healing process, stimulating re-epithelization and collagen maturation, increasing breaking strength and significantly augmenting the number of new vessels, as indicated by PECAM-1 immunostaining. However, Ang-1 gene transfer did not modify the decrease in VEGF mRNA and protein expression in diabetic mice; in contrast, Ang-1 increased eNOS expression and augmented nitrate wound content and VEGFR-2 immunostaining and protein expression. Ang-1 gene transfer did not change vascular permeability. Similar results were obtained in normoglycaemic animals. In conclusion, our results provide strong evidence that Ang-1 gene transfer improves the delayed wound repair in diabetes by inducing angiogenesis in a VEGF-independent manner.

scholarly journals Relaxin improves multiple markers of wound healing and ameliorates the disturbed healing pattern of genetically diabetic mice

2013 ◽  
Vol 125 (12) ◽  
pp. 575-585 ◽  
Author(s):  
Alessandra Bitto ◽  
Natasha Irrera ◽  
Letteria Minutoli ◽  
Margherita Calò ◽  
Patrizia Lo Cascio ◽  
...  
Keyword(s):  
Wound Healing ◽  
Breaking Strength ◽  
Histological Evaluation ◽  
Concomitant Treatment ◽  
Diabetic Mice ◽  
Vegf Mrna ◽  
Impaired Wound Healing ◽  
Wound Model ◽  
Stromal Cell Derived Factor ◽  
Genetically Diabetic Mice

Diabetic mice are characterized by a disrupted expression pattern of VEGF (vascular endothelial growth factor), and impaired vasculogenesis during healing. Experimental evidence suggests that RLX (relaxin) can improve several parameters associated with wound healing. Therefore we investigated the effects of porcine-derived RLX in diabetes-related wound-healing defects in genetically diabetic mice. An incisional wound model was produced on the back of female diabetic C57BL/KsJ-m+/+Leptdb (db+/db+) mice and their normal littermates (db+/+m). Animals were treated daily with porcine RLX (25 μg/mouse per day, subcutaneously) or its vehicle. Mice were killed on 3, 6 and 12 days after skin injury for measurements of VEGF mRNA and protein synthesis, SDF-1α (stromal cell-derived factor-1α) mRNA and eNOS (endothelial NO synthase) expression. Furthermore, we evaluated wound-breaking strength, histological changes, angiogenesis and vasculogenesis at day 12. Diabetic animals showed a reduced expression of VEGF, eNOS and SDF-1α compared with non-diabetic animals. At day 6, RLX administration resulted in an increase in VEGF mRNA expression and protein wound content, in eNOS expression and in SDF-1α mRNA. Furthermore, the histological evaluation indicated that RLX improved the impaired wound healing, enhanced the staining of MMP-11 (matrix metalloproteinase-11) and increased wound-breaking strength at day 12 in diabetic mice. Immunohistochemistry showed that RLX in diabetic animals augmented new vessel formation by stimulating both angiogenesis and vasculogenesis. RLX significantly reduced the time to complete skin normalization and this effect was abrogated by a concomitant treatment with antibodies against VEGF and CXCR4 (CXC chemokine receptor 4), the SDF-1α receptor. These data strongly suggest that RLX may have a potential application in diabetes-related wound disorders.

scholarly journals Keratin Scaffolds Containing Casomorphin Stimulate Macrophage Infiltration and Accelerate Full-Thickness Cutaneous Wound Healing in Diabetic Mice

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2554
Author(s):  
Marek Konop ◽  
Anna K. Laskowska ◽  
Mateusz Rybka ◽  
Ewa Kłodzińska ◽  
Dorota Sulejczak ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Dressing ◽  
Healing Process ◽  
Skin Wound ◽  
Wound Healing Process ◽  
Diabetic Mice ◽  
Full Thickness ◽  
Skin Wound Healing ◽  
Impaired Wound Healing

Impaired wound healing is a major medical challenge, especially in diabetics. Over the centuries, the main goal of tissue engineering and regenerative medicine has been to invent biomaterials that accelerate the wound healing process. In this context, keratin-derived biomaterial is a promising candidate due to its biocompatibility and biodegradability. In this study, we evaluated an insoluble fraction of keratin containing casomorphin as a wound dressing in a full-thickness surgical skin wound model in mice (n = 20) with iatrogenically induced diabetes. Casomorphin, an opioid peptide with analgesic properties, was incorporated into keratin and shown to be slowly released from the dressing. An in vitro study showed that keratin-casomorphin dressing is biocompatible, non-toxic, and supports cell growth. In vivo experiments demonstrated that keratin-casomorphin dressing significantly (p < 0.05) accelerates the whole process of skin wound healing to the its final stage. Wounds covered with keratin-casomorphin dressing underwent reepithelization faster, ending up with a thicker epidermis than control wounds, as confirmed by histopathological and immunohistochemical examinations. This investigated dressing stimulated macrophages infiltration, which favors tissue remodeling and regeneration, unlike in the control wounds in which neutrophils predominated. Additionally, in dressed wounds, the number of microhemorrhages was significantly decreased (p < 0.05) as compared with control wounds. The dressing was naturally incorporated into regenerating tissue during the wound healing process. Applied keratin dressing favored reconstruction of more regular skin structure and assured better cosmetic outcome in terms of scar formation and appearance. Our results have shown that insoluble keratin wound dressing containing casomorphin supports skin wound healing in diabetic mice.

Angiopoietin-1 and -2 mRNA and protein expression in mouse preimplantation embryos and uteri suggests a role in angiogenesis during implantation

2006 ◽  
Vol 18 (5) ◽  
pp. 509 ◽  
Author(s):  
A. P. Hess ◽  
J. Hirchenhain ◽  
A. Schanz ◽  
S. Talbi ◽  
A. E. Hamilton ◽  
...  
Keyword(s):  
Protein Expression ◽  
Embryo Implantation ◽  
Mouse Embryos ◽  
Preimplantation Embryos ◽  
Preimplantation Mouse Embryos ◽  
Preimplantation Mouse ◽  
Mrna And Protein Expression ◽  
Implantation Process ◽  
Endometrial Epithelium ◽  
Angiopoietin 1

After attachment and migration through the endometrial epithelium, the embryo must induce angiogenesis within the endometrial stroma to successfully complete the implantation process. Growth factors have been shown to play an important role in embryo implantation and placentation. The aim of the study was to investigate the expression of angiopoietin-1 and -2 (Ang-1 and -2) mRNA and protein expression during the development of single preimplantation mouse embryos and of possible complementary expression in mouse uteri. Angiopoietin-1 mRNA was expressed throughout development in 78% of zygotes, 66% of 2-cell-embryos, 71% of 4-cell-embryos, 70% of 8-cell-embryos, 60% of morula stages, 48% of early blastocysts and 78% of late blastocysts. The number of Ang-1-expressing embryos in the early-blastocyst group was significantly different in comparison with zygotes, 4-cell-embryos, 8-cell-embryos and late blastocysts. Angiopoietin-2 mRNA and protein expression could not be detected in preimplantation embryos. Examination of the uteri revealed Ang-2 mRNA and protein expression in the oestrogen-dominated cycling phase and the progesterone-dominated mated phase, whereas Ang-1 expression was restricted to the mated phase. Herein, Ang-1 expression in preimplantation mouse embryos as well as Ang-1 and -2 expression in mouse uteri is demonstrated, suggesting a possible role for angiopoietins in the embryo–maternal dialogue of the implantation process via an enhancement of the vascular remodelling in favour of an implanting conceptus.

Quercetin and its Natural Sources in Wound Healing Management

2019 ◽  
Vol 26 (31) ◽  
pp. 5825-5848 ◽  
Author(s):  
Nicoletta Polera ◽  
Mariateresa Badolato ◽  
Filomena Perri ◽  
Gabriele Carullo ◽  
Francesca Aiello
Keyword(s):  
Wound Healing ◽  
Wound Repair ◽  
Chronic Wounds ◽  
Wound Care ◽  
Biological Activities ◽  
Healing Process ◽  
Wound Management ◽  
Wound Healing Process ◽  
Impaired Wound Healing ◽  
Care Research

Giving a glance to the report of Wound Care Market by Product updated in 2017, we can see that wound care market is expected to reach USD 22.01 billion by 2022 from USD 18.35 billion at a CAGR of 3.7%. Numerous factors are driving the growth of this market, including the increasing prevalence of chronic wounds and acute wounds, increasing aged population, rising R&D activities and advancement in the field of wound care research. Advanced wound management products are accounted for the largest market share in 2017. These evidences mean that the wound care research represents a Clinical Emergency other than an interesting Marketing tool. Drug therapies so far fight efficaciously with the opportunistic pathologies derived from chronic wounds, although an unsolved challenge is still finding a useful remedy to correct the impaired wound healing process and overcome the chronic wound state, to avoid bacterial rising and severe pain. Traditional medicinal plants have been widely used in the management of wounds and different plant extracts have been evaluated for their wound healing properties through both in vitro and in vivo studies. Their phytochemical components in particular quercetin, contribute to their remedial properties in wound repair. Quercetin has important biological activities related to the improvement of the wound healing process. The present review discusses and focuses on the latest findings of the wound healing properties of quercetin, alone or as a part of plant extract, and its role as a new frontier in wound repair.

scholarly journals Vitamin D Ameliorates Impaired Wound Healing in Streptozotocin-Induced Diabetic Mice by Suppressing Endoplasmic Reticulum Stress

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Yi Feng Yuan ◽  
Sushant K. Das ◽  
Mao Quan Li
Keyword(s):  
Vitamin D ◽  
Wound Healing ◽  
Cell Viability ◽  
Er Stress ◽  
Umbilical Vein ◽  
Healing Process ◽  
Vitamin D Supplementation ◽  
Diabetic Mice ◽  
Impaired Wound Healing ◽  
Apoptosis Rate

Background. This study is designed to investigate whether vitamin D promotes diabetic wound healing and explore the potential mechanism which may be involved in the healing process. Material and Methods. Human umbilical vein endothelial cells (HUVECs) were treated with 200 μg/ml of advanced glycation end product-modified human serum albumin (AGE-HSA) and 250 mg/dl of glucose with vitamin D. Cell viability was analyzed using the CCK-8 assay, and the apoptosis rate was measured using flow cytometry. Endogenous markers of ER stress were quantified using Western blot and a real-time polymerase chain reaction. Diabetic mice were treated with vitamin D (100 ng/kg per day) for 14 days. The ulcer area and ulcerative histology were detected dynamically. Results. Vitamin D administration not only decreased the apoptosis rate but also increased cell viability. Furthermore, the expression of endogenous markers of ER stress was downregulated as a result of vitamin D treatment. Vitamin D supplementation significantly accelerated wound healing of diabetic mice and improved the healing quality. Further studies showed that reduced ER stress was associated with the positive outcome. Conclusion. These results suggest that vitamin D may ameliorate impaired wound healing in diabetic mice by suppressing ER stress.

Activation of adenosine A2A receptors restores the altered cell-cycle machinery during impaired wound healing in genetically diabetic mice

Surgery ◽  
2011 ◽  
Vol 149 (2) ◽  
pp. 253-261 ◽  
Author(s):  
Domenica Altavilla ◽  
Francesco Squadrito ◽  
Francesca Polito ◽  
Natasha Irrera ◽  
Margherita Calò ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Wound Healing ◽  
Diabetic Mice ◽  
Adenosine A2a Receptors ◽  
Impaired Wound Healing ◽  
A2a Receptors ◽  
Genetically Diabetic Mice ◽  
Altered Cell ◽  
Adenosine A2a ◽  
Cell Cycle Machinery

scholarly journals Effect of two photobiomodulation devices on the tissue repair of mice

2019 ◽  
Author(s):  
Jacks Jorge Junior ◽  
Ariane Victoria de Gaspari ◽  
Felipe Franco ◽  
Julia Cirqueira Neves ◽  
Lucas Augustinho Trevisan ◽  
...  
Keyword(s):  
Tissue Repair ◽  
Wound Repair ◽  
Healing Process ◽  
Alternative Therapy ◽  
Polarized Light ◽  
Skin Wounds ◽  
Diabetic Mice ◽  
Control Groups ◽  
Biologic Process ◽  
Three Phases

Cronic wounds are one of the most serious complications in individuals with diabetes. Wound repair is a complex and dynamic biologic process with three phases: inflammation, proliferation and maturation. Photobiomodulation (PBM) can be used as an alternative therapy to treat this lesion. In this study, we evaluated the effect of two PBM devices (DUAL pen and Polarized light) to treat skin wounds in diabetic mice. Mice were treated for 1 or 3 days. After treatment, all animals were sacrificed and a biopsy of the lesion was taken. Clinically, the groups treated with the two devices presented an improved healing process than control groups.

scholarly journals Beneficial Effects of Deoxyshikonin on Delayed Wound Healing in Diabetic Mice

2018 ◽  
Vol 19 (11) ◽  
pp. 3660 ◽  
Author(s):  
Jun Park ◽  
Myoung-Sook Shin ◽  
Gwi Hwang ◽  
Noriko Yamabe ◽  
Jeong-Eun Yoo ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Repair ◽  
Umbilical Vein ◽  
Sesame Seed ◽  
Tube Formation ◽  
Skin Wound ◽  
Diabetic Mice ◽  
Impaired Wound Healing ◽  
Beneficial Effects ◽  
Wide Range

Shiunko ointment is composed of five ingredients including Lithospermi Radix (LR), Angelicae Gigantis Radix, sesame seed oil, beeswax, and swine oil. It is externally applied as a treatment for a wide range of skin conditions such as eczema, psoriasis, hair loss, burns, topical wounds, and atopic dermatitis. Deoxyshikonin is the major angiogenic compound extracted from LR. In this study, we investigated the efficacy of LR extract and deoxyshikonin on impaired wound healing in streptozotocin (STZ)-induced diabetic mice. Treatment with LR extract elevated tube formation in human umbilical vein endothelial cells (HUVECs) and exerted antioxidant activity. An open skin wound was produced on the backs of diabetic mice and was then topically treated with deoxyshikonin or vehicle. In addition, deoxyshikonin promoted tube formation in high glucose conditions exposed to HUVECs, and which may be regulated by increased VEGFR2 expression and phosphorylation of Akt and p38. Our results demonstrate that deoxyshikonin application promoted wound repair in STZ-induced diabetic mice. Collectively, these data suggest that deoxyshikonin is an active ingredient of LR, thereby contributing to wound healing in patients with diabetes.

Sign in / Sign up

Export Citation Format

Share Document