Live imaging of Smad2/3 signaling in mouse skin wound healing

Although various pharmacological activities of the shikonins have been documented, understanding the hierarchical regulation of these diverse bioactivities at the genome level is unsubstantiated. In this study, through cross examination between transcriptome and microRNA array analyses, we predicted that topical treatment of shikoninin vivoaffects epithelial-mesenchymal transition (EMT) and the expression of related microRNAs, including 200a, 200b, 200c, 141, 205, and 429 microRNAs, in mouse skin tissues.In situimmunohistological analyses further demonstrated that specific EMT regulatory molecules are enhanced in shikonin-treated epidermal tissues. RT-PCR analyses subsequently confirmed that shikonin treatment downregulated expression of microRNA-205 and other members of the 200 family microRNAs. Further, expression of two RNA targets of the 200 family microRNAs in EMT regulation, Sip1 (Zeb2) and Tcf8 (Zeb1), was consistently upregulated by shikonin treatment. Enhancement of these EMT activities was also detected in shikonin-treated wounds, which repaired faster than controls. These results suggest that topical treatment with shikonin can confer a potent stimulatory effect on EMT and suppress the expression of the associated microRNAs in skin wound healing. Collectively, these cellular and molecular data provide further evidence in support of our previous findings on the specific pharmacological effects of shikonin in wound healing and immune modulation.

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Apoptotic bodies derived from mesenchymal stem cells promote cutaneous wound healing via regulating the functions of macrophages

Stem Cell Research & Therapy ◽

10.1186/s13287-020-02014-w ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Jin Liu ◽

Xinyu Qiu ◽

Yajie Lv ◽

Chenxi Zheng ◽

Yan Dong ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Mesenchymal Stem Cells ◽

Mouse Skin ◽

Skin Wound ◽

Therapeutic Effects ◽

Cutaneous Wound Healing ◽

Apoptotic Bodies ◽

Skin Wound Healing ◽

Cutaneous Wound

Abstract Background As the major interface between the body and the external environment, the skin is liable to various injuries. Skin injuries often lead to severe disability, and the exploration of promising therapeutic strategies is of great importance. Exogenous mesenchymal stem cell (MSC)-based therapy is a potential strategy due to the apparent therapeutic effects, while the underlying mechanism is still elusive. Interestingly, we observed the extensive apoptosis of exogenous bone marrow mesenchymal stem cells (BMMSCs) in a short time after transplantation in mouse skin wound healing models. Considering the roles of extracellular vesicles (EVs) in intercellular communication, we hypothesized that the numerous apoptotic bodies (ABs) released during apoptosis may partially contribute to the therapeutic effects. Methods ABs derived from MSCs were extracted, characterized, and applied in mouse skin wound healing models, and the therapeutic effects were evaluated. Then, the target cells of ABs were explored, and the effects of ABs on macrophages were investigated in vitro. Results We found ABs derived from MSCs promoted cutaneous wound healing via triggering the polarization of macrophages towards M2 phenotype. In addition, the functional converted macrophages further enhanced the migration and proliferation abilities of fibroblasts, which together facilitated the wound healing process. Conclusions Collectively, our study demonstrated that transplanted MSCs promoted cutaneous wound healing partially through releasing apoptotic bodies which could convert the macrophages towards an anti-inflammatory phenotype that plays a crucial role in the tissue repair process.

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Neutrophils Express Tumor Necrosis Factor-α During Mouse Skin Wound Healing

Journal of Investigative Dermatology ◽

10.1111/1523-1747.ep12313429 ◽

1995 ◽

Vol 105 (1) ◽

pp. 120-123 ◽

Cited By ~ 45

Author(s):

Elles Feiken ◽

John Rømer ◽

Jens Eriksen ◽

Leif R. Lund

Keyword(s):

Wound Healing ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Mouse Skin ◽

Skin Wound ◽

Skin Wound Healing ◽

Factor Α ◽

Necrosis Factor

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Scarless wound repair: a human fetal skin model

Development ◽

10.1242/dev.114.1.253 ◽

1992 ◽

Vol 114 (1) ◽

pp. 253-259 ◽

Cited By ~ 2

Author(s):

H.P. Lorenz ◽

M.T. Longaker ◽

L.A. Perkocha ◽

R.W. Jennings ◽

M.R. Harrison ◽

...

Keyword(s):

Wound Healing ◽

Gestational Age ◽

Animal Studies ◽

Wound Repair ◽

Mouse Skin ◽

Skin Wound ◽

Scar Formation ◽

Fetal Skin ◽

Skin Wound Healing ◽

Thickness Skin

Animal studies demonstrate that the fetus heals cutaneous wounds by reformation of normal tissue architecture without scar formation. We have developed a new model to study human fetal skin wound healing. Grafts of human fetal skin placed onto athymic mice retain the morphologic features of normal development, although they differentiate at an accelerated rate when placed cutaneously compared to subcutaneously. Full-thickness skin grafts from human fetuses at 15 (n = 12), 17 (n = 11), 18 (n = 25), 19 (n = 20) and 22 (n = 13) weeks gestational age were placed onto athymic (nu/nu) mice in 2 locations: (1) cutaneously onto a fascial bed and thereby exposed to air or (2) subcutaneously in a pocket under the murine panniculus carnosus. Linear incisions were made in each graft 7 days after transplantation. Grafts were harvested at 7, 14 and 21 days postwounding and analyzed histologically for scar formation. By hematoxylin & eosin and Mallory's trichrome stains, complete epidermal and dermal graft wound healing without scar formation was demonstrated in the subcutaneous grafts at each gestational age studied. In contrast, scar was seen at all time points in the cutaneous grafts in both the incisional wound and at the interface of the fetal human skin graft and adult mouse skin, regardless of fetal skin gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)

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Increased glucocorticoid activation during mouse skin wound healing

Journal of Endocrinology ◽

10.1530/joe-13-0420 ◽

2014 ◽

Vol 221 (1) ◽

pp. 51-61 ◽

Cited By ~ 23

Author(s):

Ana Tiganescu ◽

Melanie Hupe ◽

Yoshikazu Uchida ◽

Theodora Mauro ◽

Peter M Elias ◽

...

Keyword(s):

Wound Healing ◽

Wound Repair ◽

De Novo ◽

Mouse Skin ◽

Inflammatory Cells ◽

Skin Wound ◽

Skin Wound Healing ◽

Variable Expression ◽

Before And After

Glucocorticoid (GC) excess inhibits wound healing causing increased patient discomfort and infection risk. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activates GCs (converting 11-dehydrocorticosterone to corticosterone in rodents) in many tissues including skin, wherede novosteroidogenesis from cholesterol has also been reported. To examine the regulation of 11β-HSD1 and steroidogenic enzyme expression during wound healing, 5 mm wounds were generated in female SKH1 mice and compared at days 0, 2, 4, 8, 14, and 21 relative to unwounded skin. 11β-HSD1 expression (mRNA and protein) and enzyme activity were elevated at 2 and 4 days post-wounding, with 11β-HSD1 localizing to infiltrating inflammatory cells. 11β-HSD2 (GC-deactivating) mRNA expression and activity were undetectable. Although several steroidogenic enzymes displayed variable expression during healing, expression of the final enzyme required for the conversion of 11-deoxycorticosterone to corticosterone, 11β-hydroxylase (CYP11B1), was lacking in unwounded skin and post-wounding. Consequently, 11-deoxycorticosterone was the principal progesterone metabolite in mouse skin before and after wounding. Our findings demonstrate that 11β-HSD1 activates considerably more corticosterone than is generatedde novofrom progesterone in mouse skin and drives GC exposure during healing, demonstrating the basis for 11β-HSD1 inhibitors to accelerate wound repair.

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Correction: Fibromodulin-Deficiency Alters Temporospatial Expression Patterns of Transforming Growth Factor-β Ligands and Receptors during Adult Mouse Skin Wound Healing

PLoS ONE ◽

10.1371/journal.pone.0246557 ◽

2021 ◽

Vol 16 (1) ◽

pp. e0246557

Author(s):

Keyword(s):

Wound Healing ◽

Growth Factor ◽

Adult Mouse ◽

Transforming Growth Factor ◽

Expression Patterns ◽

Mouse Skin ◽

Transforming Growth Factor Β ◽

Skin Wound ◽

Skin Wound Healing

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Nanospheres Loaded with Curcumin Improve the Bioactivity of Umbilical Cord Blood-Mesenchymal Stem Cells via c-Src Activation during the Skin Wound Healing Process

Cells ◽

10.3390/cells9061467 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1467

Author(s):

Do-Wan Kim ◽

Chang-Hyung Choi ◽

Jong Pil Park ◽

Sei-Jung Lee

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Mesenchymal Stem Cells ◽

Cord Blood ◽

Umbilical Cord Blood ◽

Healing Process ◽

Mouse Skin ◽

Skin Wound ◽

Wound Healing Process ◽

Skin Wound Healing

Curcumin, a hydrophobic polyphenol derived from turmeric, has been used a food additive and as a herbal medicine for the treatment of various diseases, but the clinical application of curcumin is restricted by its poor aqueous solubility and its low permeability and bioavailability levels. In the present study, we investigate the functional role of a nanosphere loaded with curcumin (CN) in the promotion of the motility of human mesenchymal stem cells (MSCs) during the skin wound healing process. CN significantly increased the motility of umbilical cord blood (UCB)-MSCs and showed 10,000-fold greater migration efficacy than curcumin. CN stimulated the phosphorylation of c-Src and protein kinase C which are responsible for the distinctive activation of the MAPKs. Interestingly, CN significantly induced the expression levels of α-actinin-1, profilin-1 and filamentous-actin, as regulated by the phosphorylation of nuclear factor-kappa B during its promotion of cell migration. In a mouse skin excisional wound model, we found that transplantation of UCB-MSCs pre-treated with CN enhanced wound closure, granulation, and re-epithelialization at mouse skin wound sites. These results indicate that CN is a functional agent that promotes the mobilization of UCB-MSCs for cutaneous wound repair.

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Indirubin-pregnane X receptor-JNK axis accelerates skin wound healing

Scientific Reports ◽

10.1038/s41598-019-54754-2 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Yuka Tanaka ◽

Hiroshi Uchi ◽

Takamichi Ito ◽

Masutaka Furue

Keyword(s):

Wound Healing ◽

Wound Closure ◽

Mouse Skin ◽

Pregnane X Receptor ◽

Skin Wound ◽

Skin Ulcer ◽

Luciferase Reporter ◽

Skin Wound Healing ◽

Jnk Pathway ◽

Ulcer Model

AbstractIndirubin is a potent anti-inflammatory phytochemical derived from indigo naturalis. It is also endogenously produced in the intestine and detected in the circulation in mammals. Indirubin exerts its biological functions via two xenobiotic receptor systems: aryl hydrocarbon receptor (AHR) and pregnane X receptor (PXR); however, its effects on wound healing remain elusive. To investigate whether indirubin promotes wound healing, we utilized an in vitro scratch injury assay and in vivo full-thickness mouse skin ulcer model and assessed wound closure. Indirubin significantly accelerated wound closure in both the scratch assay and the skin ulcer model. Using inhibitors of cell proliferation or migration, indirubin was found to upregulate the migratory but not the proliferative capacity of keratinocytes. Activation of AHR/PXR by indirubin was confirmed by their nuclear translocation and subsequent upregulation of CYP1A1 (AHR), or UGT1A1 mRNA (PXR) and also by luciferase reporter assay (PXR). Although both AHR and PXR were activated by indirubin, its pro-migratory capacity was canceled by PXR inhibition but not by AHR inhibition and was dependent on the JNK pathway. Moreover, activated PXR was detected in the nuclei of re-epithelialized keratinocytes in human skin ulcers. In conclusion, this study shows that the indirubin-PXR-JNK pathway promotes skin wound healing.

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