Apoptosis is increased in a model of diabetes-impaired wound healing in genetically diabetic mice

1997 ◽  
Vol 29 (1) ◽  
pp. 191-200 ◽  
Author(s):  
Ian A. Darby ◽  
Teresa Bisucci ◽  
Tim D. Hewitson ◽  
Donald G. MacLellan
Keyword(s):  
Wound Healing ◽  
Diabetic Mice ◽  
Impaired Wound Healing ◽  
Genetically Diabetic Mice

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.

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 A small molecule HIF-1α stabilizer that accelerates diabetic wound healing

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Guodong Li ◽  
Chung-Nga Ko ◽  
Dan Li ◽  
Chao Yang ◽  
Wanhe Wang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Small Molecule ◽  
Hypoxia Inducible Factor ◽  
Diabetic Patients ◽  
Diabetic Mice ◽  
Impaired Wound Healing ◽  
Von Hippel Lindau ◽  
Design And Synthesis

AbstractImpaired wound healing and ulcer complications are a leading cause of death in diabetic patients. In this study, we report the design and synthesis of a cyclometalated iridium(III) metal complex 1a as a stabilizer of hypoxia-inducible factor-1α (HIF-1α). In vitro biophysical and cellular analyses demonstrate that this compound binds to Von Hippel-Lindau (VHL) and inhibits the VHL–HIF-1α interaction. Furthermore, the compound accumulates HIF-1α levels in cellulo and activates HIF-1α mediated gene expression, including VEGF, GLUT1, and EPO. In in vivo mouse models, the compound significantly accelerates wound closure in both normal and diabetic mice, with a greater effect being observed in the diabetic group. We also demonstrate that HIF-1α driven genes related to wound healing (i.e. HSP-90, VEGFR-1, SDF-1, SCF, and Tie-2) are increased in the wound tissue of 1a-treated diabetic mice (including, db/db, HFD/STZ and STZ models). Our study demonstrates a small molecule stabilizer of HIF-1α as a promising therapeutic agent for wound healing, and, more importantly, validates the feasibility of treating diabetic wounds by blocking the VHL and HIF-1α interaction.

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.

Improvement in wound healing by a novel synthetic collagen-gel dressing in genetically diabetic mice

2010 ◽  
Vol 22 (2) ◽  
pp. 61-67 ◽  
Author(s):  
Daichi Chikazu ◽  
Tetsushi Taguchi ◽  
Hiroyuki Koyama ◽  
Hisako Hikiji ◽  
Hisako Fujihara ◽  
...  
Keyword(s):  
Wound Healing ◽  
Collagen Gel ◽  
Diabetic Mice ◽  
Genetically Diabetic Mice

scholarly journals Systemic administration of high-molecular weight hyaluronan stimulates wound healing in genetically diabetic mice

2011 ◽  
Vol 1812 (7) ◽  
pp. 752-759 ◽  
Author(s):  
Mariarosaria Galeano ◽  
Francesca Polito ◽  
Alessandra Bitto ◽  
Natasha Irrera ◽  
Giuseppe M. Campo ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Wound Healing ◽  
High Molecular Weight ◽  
Systemic Administration ◽  
Diabetic Mice ◽  
Genetically Diabetic Mice

scholarly journals A Synthetic Curcuminoid Analog, (2E,6E)-2,6-bis(2-(trifluoromethyl)benzylidene)cyclohexanone, Ameliorates Impaired Wound Healing in Streptozotocin-Induced Diabetic Mice by Increasing miR-146a

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 920
Author(s):  
Jingjuan Huang ◽  
Jia Fu ◽  
Bing Liu ◽  
Rui Wang ◽  
Tianhui You
Keyword(s):  
Wound Healing ◽  
Umbilical Vein ◽  
Interleukin 1 ◽  
Diabetic Wound ◽  
Diabetic Mice ◽  
Skin Wound Healing ◽  
Promising Alternative ◽  
Impaired Wound Healing ◽  
Diabetic Wound Healing

The impairment in diabetic wound healing represents a significant clinical problem, with no efficient targeted treatments for these wound disorders. Curcumin is well confirmed to improve diabetic wound healing, however, its low bioavailability and poor solubility severely limit its clinical application. This study aims to provide the pharmacological basis for the use of (2E,6E)-2,6-bis(2-(trifluoromethyl)benzylidene)cyclohexanone (C66). The results showed that topically applied C66 improved cutaneous wound healing in vivo. Further studies showed that C66 treatment increased the level of microRNA-146a (miR-146a) in the wounds in streptozotocin (STZ)-induced diabetic mice, downregulated the expression of interleukin-1 receptor-associated kinase 1 (IRAK1) and phosphorylated nuclear factor-κB (NF-κB) p65 subunit (p-p65) (both p < 0.05), and suppressed the mRNA expression of inflammation-related cytokines, tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), and interleukin-6 (IL-6). The in vitro data obtained in human umbilical vein endothelial cells (HUVECs) showed that C66 could reverse high glucose (HG)-induced NF-κB activation due to upregulation of miR-146a expression, which matched the in vivo findings. In conclusion, the present study indicates that C66 exerts anti-inflammation activity and accelerates skin wound healing of diabetic mice, probably via increasing miR-146a and inhibiting the NF-κB-mediated inflammation pathway. Therefore, C66 may be a promising alternative for the treatment of diabetic wounds.

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