Liver is a Primary Source of Insulin-like Growth Factor-1 in Skin Wound Healing

2021 ◽  
Author(s):  
Rita E Roberts ◽  
Jacqueline Cavalcante Silva ◽  
Rhonda D Kineman ◽  
Timothy J Koh

Insulin-like growth factor (IGF)-1 plays important roles in tissue repair through its ability to stimulate wound cell activity. While IGF-1 is expressed locally by wound cells, liver-derived IGF-1 is also present at high levels in the circulation, and the contributions of local versus circulating IGF-1 to wound levels remain undefined. The hypothesis of this study was that liver is a primary source of IGF-1 during skin wound healing. To test this hypothesis, we utilized a model that allows inducible ablation of IGF-1 specifically in liver of adult mice. We demonstrate that ablation of liver IGF-1 leads to >85% loss of circulating IGF-1 and ~60% decrease in wound IGF-1 during the proliferative phase of healing in both male and female mice. This reduction of liver-derived IGF-1 did not alter local mRNA expression of IGF-1 in wounds. Knockdown of liver IGF-1 significantly delayed wound re-epithelialization, and reduced granulation tissue formation and collagen deposition. Knockdown of liver IGF-1 also significantly reduced angiogenesis and resulted in persistent macrophage accumulation. In summary, liver is a primary source of IGF-1 in skin wounds, and contributes to many aspects of both epithelial and dermal healing.

PLoS ONE ◽  
2018 ◽  
Vol 13 (3) ◽  
pp. e0193084 ◽  
Author(s):  
Ileana Ruxandra Botusan ◽  
Xiaowei Zheng ◽  
Sampath Narayanan ◽  
Jacob Grünler ◽  
Vivekananda Gupta Sunkari ◽  
...  

2020 ◽  
Vol 8 ◽  
Author(s):  
Pengcheng Xu ◽  
Yaguang Wu ◽  
Lina Zhou ◽  
Zengjun Yang ◽  
Xiaorong Zhang ◽  
...  

Abstract Background Autologous platelet-rich plasma (PRP) has been suggested to be effective for wound healing. However, evidence for its use in patients with acute and chronic wounds remains insufficient. The aims of this study were to comprehensively examine the effectiveness, synergy and possible mechanism of PRP-mediated improvement of acute skin wound repair. Methods Full-thickness wounds were made on the back of C57/BL6 mice. PRP or saline solution as a control was administered to the wound area. Wound healing rate, local inflammation, angiogenesis, re-epithelialization and collagen deposition were measured at days 3, 5, 7 and 14 after skin injury. The biological character of epidermal stem cells (ESCs), which reflect the potential for re-epithelialization, was further evaluated in vitro and in vivo. Results PRP strongly improved skin wound healing, which was associated with regulation of local inflammation, enhancement of angiogenesis and re-epithelialization. PRP treatment significantly reduced the production of inflammatory cytokines interleukin-17A and interleukin-1β. An increase in the local vessel intensity and enhancement of re-epithelialization were also observed in animals with PRP administration and were associated with enhanced secretion of growth factors such as vascular endothelial growth factor and insulin-like growth factor-1. Moreover, PRP treatment ameliorated the survival and activated the migration and proliferation of primary cultured ESCs, and these effects were accompanied by the differentiation of ESCs into adult cells following the changes of CD49f and keratin 10 and keratin 14. Conclusion PRP improved skin wound healing by modulating inflammation and increasing angiogenesis and re-epithelialization. However, the underlying regulatory mechanism needs to be investigated in the future. Our data provide a preliminary theoretical foundation for the clinical administration of PRP in wound healing and skin regeneration.


2020 ◽  
Vol 21 (14) ◽  
pp. 4952 ◽  
Author(s):  
Fernando Pereira Beserra ◽  
Lucas Fernando Sérgio Gushiken ◽  
Ana Júlia Vieira ◽  
Danilo Augusto Bérgamo ◽  
Patrícia Luísa Bérgamo ◽  
...  

Skin wound healing is a highly complex event that involves different mediators at the cellular and molecular level. Lupeol has been reported to possess different biological activities, such as anti-inflammatory, antioxidant, antidiabetic, and in vitro wound healing properties, which motivated us to proceed with in vivo studies. We aimed to investigate the wound healing effect of lupeol-based cream for 3, 7, and 14 days. Wound excisions were induced on the thoraco-lumbar region of rats and topically treated immediately after injury induction. Macroscopic, histopathological, and immunohistochemical analyses were performed. Cytokine levels were measured by ELISA and gene expression was evaluated by real-time RT-qPCR. Our results showed a strong wound-healing effect of lupeol-based cream after 7 and 14 days. Lupeol treatment caused a reduction in proinflammatory cytokines (TNF-a, IL-1β, and IL-6) and gene and protein NF-κB expression, and positively altered IL-10 levels, showing anti-inflammatory effects in the three treatment periods. Lupeol treatment showed involvement in the proliferative phase by stimulating the formation of new blood vessels, increasing the immunostaining of Ki-67 and gene expression, and immunolabeling of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF), and increasing gene expression of transforming growth factor beta-1 (TGF-β1) after seven days of treatment. Lupeol was also involved in the tissue regeneration phase by increasing the synthesis of collagen fibers noted in the three treatment periods analyzed. Our findings suggest that lupeol may serve as a novel therapeutic option to treat cutaneous wounds by regulating mechanisms involved in the inflammatory, proliferative, and tissue-remodeling phases.


2015 ◽  
Vol 4 (8) ◽  
pp. 479-489 ◽  
Author(s):  
Priscilla S. Briquez ◽  
Jeffrey A. Hubbell ◽  
Mikaël M. Martino

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Bo Zhou ◽  
Jianan Ren ◽  
Chao Ding ◽  
Yin Wu ◽  
Dong Hu ◽  
...  

Objective.The purposes of our present study were to evaluate the potential of platelet-rich plasma gel to enhance granulation tissue formation after open abdomen and to examine whether the effect was attributable to stimulating rapid neovascularization.Methods.Twenty-four rats underwent colon ascendens stent peritonitis surgery to induce sepsis, followed by intraperitoneal injection of nitrogen to create intra-abdominal hypertension. Four hours later, laparotomies were performed. The rats were randomized into three groups (n=8for each group): control, platelet-poor plasma (PPP), and platelet-rich plasma (PRP) groups. One week after the treatment, granulation tissue formation and angiogenesis were evaluated by histological and laser Doppler analysis.Results.The resultant platelet count in platelet-rich plasma was higher than that of PPP. The concentrations of platelet-derived growth factor BB, transforming growth factorβ-1, and vascular endothelial growth factor in PRP were significantly higher when compared with that of PPP. Myofibroblast count, granulation tissue thickness, vessel numbers, and blood perfusion were increased in PRP group, followed by PPP group, with control being the least.Conclusion.Rapidlyin situforming platelet-rich plasma gel promoted remarkable neovascularization and early wound healing after open abdomen and may lead to novel and effective treatments for open abdominal wounds.


Author(s):  
Min Cheol Kang ◽  
Silvia Yumnam ◽  
Woo Sung Park ◽  
Hae Min So ◽  
Ki Hyun Kim ◽  
...  

Ulmus species have been widely used in Korean folk medicine because of their anti-inflammatory and antimicrobial properties. We intended to investigate the wound healing effect of the powder of Ulmus parvifolia (UP) root bark in a mouse wound healing model. We also determined the mechanisms of effects of Ulmus parvifolia (UP) in skin and skin wound healing effect using keratinocyte model. in vivo experiments showed that the wound lesions in the mice decreased by U. parvifolia with 200 mesh size of root bark powder and significantly reduced by treatment with UP, compared with those treated with U. macrocarpa (UM). Results from in vitro experiments also revealed that UP extract promoted the migration of human skin keratinocytes. UP powder treatment upregulated the expression of the matrix metalloproteinase-2 and -9 protein and significantly increased transforming growth factor (TGF)-β levels. We confirmed that topical administration of the bark powder of exerted a significant effect on skin wound healing by upregulating the expression of MMP and transforming growth factor-β. TGF-β In, Our study suggests that U. parvifolia may be a potential candidate for skin wound healing including epidermal skin rejuvernation.


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