Exosomes derived from autologous dermal fibroblasts promote diabetic cutaneous wound healing through the Akt/β-catenin pathway

Cell Cycle ◽  
2021 ◽  
Vol 20 (5-6) ◽  
pp. 616-629
Author(s):  
Xinye Han ◽  
Peipei Wu ◽  
Linli Li ◽  
Hassan Mohamud Sahal ◽  
Cheng Ji ◽  
...  
2019 ◽  
Vol 2019 ◽  
pp. 1-30 ◽  
Author(s):  
Aleksandra Shedoeva ◽  
David Leavesley ◽  
Zee Upton ◽  
Chen Fan

Cutaneous wound healing is the process by which skin repairs itself. It is generally accepted that cutaneous wound healing can be divided into 4 phases: haemostasis, inflammation, proliferation, and remodelling. In humans, keratinocytes re-form a functional epidermis (reepithelialization) as rapidly as possible, closing the wound and reestablishing tissue homeostasis. Dermal fibroblasts migrate into the wound bed and proliferate, creating “granulation tissue” rich in extracellular matrix proteins and supporting the growth of new blood vessels. Ultimately, this is remodelled over an extended period, returning the injured tissue to a state similar to that before injury. Dysregulation in any phase of the wound healing cascade delays healing and may result in various skin pathologies, including nonhealing, or chronic ulceration. Indigenous and traditional medicines make extensive use of natural products and derivatives of natural products and provide more than half of all medicines consumed today throughout the world. Recognising the important role traditional medicine continues to play, we have undertaken an extensive survey of literature reporting the use of medical plants and plant-based products for cutaneous wounds. We describe the active ingredients, bioactivities, clinical uses, formulations, methods of preparation, and clinical value of 36 medical plant species. Several species stand out, including Centella asiatica, Curcuma longa, and Paeonia suffruticosa, which are popular wound healing products used by several cultures and ethnic groups. The popularity and evidence of continued use clearly indicates that there are still lessons to be learned from traditional practices. Hidden in the myriad of natural products and derivatives from natural products are undescribed reagents, unexplored combinations, and adjunct compounds that could have a place in the contemporary therapeutic inventory.


2018 ◽  
Vol 68-69 ◽  
pp. 533-546 ◽  
Author(s):  
Mitsuaki Ono ◽  
Asuka Masaki ◽  
Azusa Maeda ◽  
Tina M. Kilts ◽  
Emilio S. Hara ◽  
...  

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Xiaoli Rong ◽  
Wenhui Chu ◽  
Haiying Zhang ◽  
Yusu Wang ◽  
Xiaoyan Qi ◽  
...  

Abstract Background When the deer antler is cast, it leaves a cutaneous wound that can achieve scarless healing due to the presence of antler stem cells (ASCs). This provides an opportunity to study regenerative wound healing. Methods In this study, we investigated the therapeutic effects and mechanism of antler stem cell-conditioned medium (ASC-CM) on cutaneous wound healing in rats. In vitro, we investigated the effects of the ASC-CM on proliferation of HUVEC and NIH-3T3 cell lines. In vivo, we evaluated the effects of ASC-CM on cutaneous wound healing using full-thickness skin punch-cut wounds in rats. Results The results showed that ASC-CM significantly stimulated proliferation of the HUVEC and NIH-3T3 cells in vitro. In vivo, completion of healing of the rat wounds treated with ASC-CM was on day 16 (± 3 days), 9 days (± 2 days) earlier than the control group (DMEM); the area of the wounds treated with ASC-CM was significantly smaller (p < 0.05) than the two control groups. Further molecular characterization showed that the ratios of Col3A1/Col1A2, TGF-β3/TGF-β1, MMP1/TIMP1, and MMP3/TIMP1 significantly increased (p < 0.01) in the healed tissue in the ASC-CM group. Conclusions In conclusion, ASC-CM effectively accelerated the wound closure rate and enhanced the quality of healing, which might be through transforming wound dermal fibroblasts into the fetal counterparts. Therefore, the ASC-CM may have potential to be developed as a novel cell-free therapeutic for scarless wound healing.


2015 ◽  
Vol 212 (7) ◽  
pp. 1061-1080 ◽  
Author(s):  
Soung-Hoon Lee ◽  
Mi-Yeon Kim ◽  
Hyun-Yi Kim ◽  
Young-Mi Lee ◽  
Heesu Kim ◽  
...  

Wnt/β-catenin signaling plays important roles in cutaneous wound healing and dermal fibrosis. However, its regulatory mechanism has not been fully elucidated, and a commercially available wound-healing agent targeting this pathway is desirable but currently unavailable. We found that CXXC-type zinc finger protein 5 (CXXC5) serves as a negative feedback regulator of the Wnt/β-catenin pathway by interacting with the Dishevelled (Dvl) protein. In humans, CXXC5 protein levels were reduced in epidermal keratinocytes and dermal fibroblasts of acute wounds. A differential regulation of β-catenin, α-smooth muscle actin (α-SMA), and collagen I by overexpression and silencing of CXXC5 in vitro indicated a critical role for this factor in myofibroblast differentiation and collagen production. In addition, CXXC5−/− mice exhibited accelerated cutaneous wound healing, as well as enhanced keratin 14 and collagen synthesis. Protein transduction domain (PTD)–Dvl-binding motif (DBM), a competitor peptide blocking CXXC5-Dvl interactions, disrupted this negative feedback loop and activated β-catenin and collagen production in vitro. Co-treatment of skin wounds with PTD-DBM and valproic acid (VPA), a glycogen synthase kinase 3β (GSK3β) inhibitor which activates the Wnt/β-catenin pathway, synergistically accelerated cutaneous wound healing in mice. Together, these data suggest that CXXC5 would represent a potential target for future therapies aimed at improving wound healing.


2020 ◽  
Vol 100 (12) ◽  
pp. 1532-1550
Author(s):  
Alevoor Srinivas Bharath Prasad ◽  
Padival Shruptha ◽  
Vijendra Prabhu ◽  
Cheruku Srujan ◽  
Usha Yogendra Nayak ◽  
...  

AbstractThe intricate biological process of cutaneous wound healing is achieved through precise and highly programmed events. Dermal fibroblasts and keratinocytes play a significant role in the process of reepithelialization during wound healing. Pathogenic bacteria such as Pseudomonas aeruginosa (P. aeruginosa) may delay the proliferative phase of wound repair by secreting their proteins leading to delayed or impaired wound healing. We have analyzed three virulent strains of P. aeruginosa isolated from the wound environment which also differed in their ability to produce biofilms. Mass spectrometric analysis of differentially expressed secreted proteins by three virulent strains of P. aeruginosa revealed peptides from pseudolysin and protease IV expressed from lasB and prpL genes. Pseudolysin and protease IV recombinant proteins were tested for their ability to modulate wound healing in several cell types of wound microenvironment in in vitro and in vivo models. Both pseudolysin and protease IV inhibited migration and survival of fibroblasts, keratinocytes, and endothelial cells. In three dimensional spheroid endothelial models and matrigel assays these proteins impeded sprouting and tube formation. In a mouse model of excision wound, pseudolysin and protease IV treatment showed reduced collagen content, inhibited neovascularization and epithelialization, and delayed wound contraction. Furthermore, pseudolysin and protease IV treatment resulted in a significant increase in plasma IL-6 levels when compared to vehicle control and control, suggesting the induction of a state of prolonged inflammation. Taken together, our data indicate pseudolysin and protease IV secreted from biofilm producing and antibiotic resistant P. aeruginosa in wound microenvironment produce both local and systemic effects that is detrimental to the maintenance of tissue homeostasis. Hence, these proteins may serve as potential therapeutic targets toward better clinical management of wounds.


2005 ◽  
Vol 53 (5) ◽  
pp. 571-581 ◽  
Author(s):  
Pauli A. Puolakkainen ◽  
Amy D. Bradshaw ◽  
Rolf A. Brekken ◽  
May J. Reed ◽  
Themis Kyriakides ◽  
...  

Secreted protein acidic and rich in cysteine (SPARC) and thrombospondin-2 (TSP-2) are structurally unrelated matricellular proteins that have important roles in cell- extracellular matrix (ECM) interactions and tissue repair. SPARC-null mice exhibit accelerated wound closure, and TSP-2-null mice show an overall enhancement in wound healing. To assess potential compensation of one protein for the other, we examined cutaneous wound healing and fibrovascular invasion of subcutaneous sponges in SPARC-TSP-2 (ST) double-null and wild-type (WT) mice. Epidermal closure of cutaneous wounds was found to occur significantly faster in ST-double-null mice, compared with WT animals: histological analysis of dermal wound repair revealed significantly more mature phases of healing at 1, 4, 7, 10, and 14 days after wounding, and electron microscopy showed disrupted ECM at 14 days in these mice. ST-double-null dermal fibroblasts displayed accelerated migration, relative to WT fibroblasts, in a wounding assay in vitro, as well as enhanced contraction of native collagen gels. Zymography indicated that fibroblasts from ST-double-null mice also produced higher levels of matrix metalloproteinase (MMP)-2. These data are consistent with the increased fibrovascular invasion of subcutaneous sponge implants seen in the double-null mice. The generally accelerated wound healing of ST-double-null mice reflects that described for the single-null animals. Importantly, the absence of both proteins results in elevated MMP-2 levels. SPARC and TSP-2 therefore perform similar functions in the regulation of cutaneous wound healing, but fine-tuning with respect to ECM production and remodeling could account for the enhanced response seen in ST-double-null mice.


Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 643-P ◽  
Author(s):  
YANFEI HAN ◽  
LINDONG LI ◽  
YANJUN LIU ◽  
YOU WANG ◽  
CHUNHUA YAN ◽  
...  

2018 ◽  
Vol 8 (2) ◽  
pp. 135-150 ◽  
Author(s):  
Anthony J. Deegan ◽  
Wendy Wang ◽  
Shaojie Men ◽  
Yuandong Li ◽  
Shaozhen Song ◽  
...  

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