scholarly journals Disease-linked connexin26 S17F promotes volar skin abnormalities and mild wound healing defects in mice

2017 ◽  
Vol 8 (6) ◽  
pp. e2845-e2845 ◽  
Author(s):  
Eric Press ◽  
Katanya C Alaga ◽  
Kevin Barr ◽  
Qing Shao ◽  
Felicitas Bosen ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Closure ◽  
Skin Diseases ◽  
Mouse Skin ◽  
Skin Wound ◽  
Keratinocyte Differentiation ◽  
Gap Junctional Intercellular Communication ◽  
Elevated Expression ◽  
And Migration ◽  
Foot Pad

Abstract Several mutant mice have been generated to model connexin (Cx)-linked skin diseases; however, the role of connexins in skin maintenance and during wound healing remains to be fully elucidated. Here we generated a novel, viable, and fertile mouse (Cx26CK14-S17F/+) with the keratitis-ichthyosis-deafness mutant (Cx26S17F) driven by the cytokeratin 14 promoter. This mutant mouse mirrors several Cx26-linked human skin pathologies suggesting that the etiology of Cx26-linked skin disease indeed stems from epidermal expression of the Cx26 mutant. Cx26CK14-S17F/+ foot pad epidermis formed severe palmoplantar keratoderma, which expressed elevated levels of Cx26 and filaggrin. Primary keratinocytes isolated from Cx26CK14-S17F/+ neonates exhibited reduced gap junctional intercellular communication and migration. Furthermore, Cx26CK14-S17F/+ mouse skin wound closure was normal but repaired epidermis appeared hyperplastic with elevated expression of cytokeratin 6. Taken together, we suggest that the Cx26S17F mutant disturbs keratinocyte differentiation and epidermal remodeling following wound closure. We further posit that Cx26 contributes to epidermal homeostasis by regulating keratinocyte differentiation, and that mice harboring a disease-linked Cx26 mutant display epidermal abnormalities yet retain most wound healing properties.

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

2019 ◽  
Vol 9 (1) ◽  
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.

scholarly journals Overexpression of the Oral Mucosa-Specific microRNA-31 Promotes Skin Wound Closure

2019 ◽  
Vol 20 (15) ◽  
pp. 3679 ◽  
Author(s):  
Lin Chen ◽  
Alyne Simões ◽  
Zujian Chen ◽  
Yan Zhao ◽  
Xinming Wu ◽  
...  
Keyword(s):  
Wound Healing ◽  
Oral Mucosa ◽  
Wound Closure ◽  
Expression Patterns ◽  
Skin Wound ◽  
Skin Wound Healing ◽  
Specific Expression ◽  
Keratinocyte Proliferation

Wounds within the oral mucosa are known to heal more rapidly than skin wounds. Recent studies suggest that differences in the microRNAome profiles may underlie the exceptional healing that occurs in oral mucosa. Here, we test whether skin wound-healing can be accelerating by increasing the levels of oral mucosa-specific microRNAs. A panel of 57 differentially expressed high expresser microRNAs were identified based on our previously published miR-seq dataset of paired skin and oral mucosal wound-healing [Sci. Rep. (2019) 9:7160]. These microRNAs were further grouped into 5 clusters based on their expression patterns, and their differential expression was confirmed by TaqMan-based quantification of LCM-captured epithelial cells from the wound edges. Of these 5 clusters, Cluster IV (consisting of 8 microRNAs, including miR-31) is most intriguing due to its tissue-specific expression pattern and temporal changes during wound-healing. The in vitro functional assays show that ectopic transfection of miR-31 consistently enhanced keratinocyte proliferation and migration. In vivo, miR-31 mimic treatment led to a statistically significant acceleration of wound closure. Our results demonstrate that wound-healing can be enhanced in skin through the overexpression of microRNAs that are highly expressed in the privileged healing response of the oral mucosa.

Fabrication of gelatin/sodium alginate-poly (3-hydroxybutyric acid) bilayer electrospun biosheet as wound healing material in nursing care on pediatric fracture surgery

2020 ◽  
pp. 152808372097634
Author(s):  
Daiqi Jiang ◽  
Zaiju Tong ◽  
Lingjun Peng ◽  
Lingzhi Zhang ◽  
Qianzi Ruan ◽  
...  
Keyword(s):  
Wound Healing ◽  
Sodium Alginate ◽  
Wound Closure ◽  
Skin Wound ◽  
Tissue Formation ◽  
Hydroxybutyric Acid ◽  
Physiochemical Properties ◽  
Pediatric Fracture ◽  
Fracture Surgery

Novel the bilayered electrospun biosheet with rapid cell mimiciking and proliferative efficacy will be suitable for wound healing application. The optimized concentration of gelatin (G) and sodium alginate (A) biosheet with nanofibrous Poly (3-hydroxybutyric acid) (P) as a bilayered elctrospun matrix through electrospinning. The engineered GAP bilayered biosheet involves tissue formation at extra cellular matrix (ECM) which further characterized its function in vitro and invivo. Here we fabricated GAP which exhibit better physiochemical properties, biological and mechanical properties with superior prosomes it enhance air passable at skin wounds. The Bilayered biosheet matrix possess better biocompatibility, cell adherence, fructuous and cell to cell interactions evaluated using cell lines. Furthermore, GAP bilayered matrix regulates growth factors to attain maximum wound closure efficiency during invivo. Thus, the fabricated GAP electrospun biosheet would be a possible wound dressing for skin wound applications.

scholarly journals Carbonic Anhydrase VI in Skin Wound Healing Study on Car6 Knockout Mice

2020 ◽  
Vol 21 (14) ◽  
pp. 5092
Author(s):  
Toini Pemmari ◽  
Jaakko Laakso ◽  
Maarit S. Patrikainen ◽  
Seppo Parkkila ◽  
Tero A. H. Järvinen
Keyword(s):  
Wound Healing ◽  
Knockout Mice ◽  
Wound Closure ◽  
Skin Wound ◽  
Carbonic Anhydrases ◽  
Skin Wound Healing ◽  
Tumor Cell Migration ◽  
Treatment Groups ◽  
Thickness Skin ◽  
Carbonic Anhydrase Vi

Carbonic anhydrases (CAs) contribute to tumor cell migration by generating an acidic environment through the conversion of carbon dioxide to bicarbonate and a proton. CA VI is secreted to milk and saliva, and it could contribute to wound closure, as a potential trophic factor, in animals that typically lick their wounds. Our aim was to investigate whether human CA VI improves skin-wound healing in full-thickness skin-wound models. The effect was studied in Car6 −/− knockout mice and wild type littermates. Half of both mice strains were given topically administered, milk-derived CA VI after wounding and eight hours later. The amount of topically given CA VI exceeded the predicted amount of natural saliva-delivered CA VI. The healing was followed for seven days and studied from photographs and histological sections. Our results showed no significant differences between the treatment groups in wound closure, re-epithelization, or granulation tissue formation, nor did the Car6 genotype affect the healing. Our results demonstrate that CA VI does not play a major role in skin-wound healing and also suggest that saliva-derived CA VI is not responsible for the licking-associated improved wound healing in animals.

In vivo Optical Coherence Tomography of Mouse Skin Wound Healing

2008 ◽  
Author(s):  
Zhijia Yuan ◽  
Julia Zakehaleva ◽  
Hugang Ren ◽  
Weiliam Chen ◽  
Yingtian Pan
Keyword(s):  
Wound Healing ◽  
Optical Coherence Tomography ◽  
Mouse Skin ◽  
Skin Wound ◽  
Optical Coherence ◽  
Skin Wound Healing

scholarly journals Effect of Combining Low Temperature Plasma, Negative Pressure Wound Therapy, and Bone Marrow Mesenchymal Stem Cells on an Acute Skin Wound Healing Mouse Model

2020 ◽  
Vol 21 (10) ◽  
pp. 3675 ◽  
Author(s):  
Hui Song Cui ◽  
So Young Joo ◽  
Yoon Soo Cho ◽  
Ji Heon Park ◽  
June-Bum Kim ◽  
...  
Keyword(s):  
Wound Healing ◽  
Combination Therapy ◽  
Wound Closure ◽  
Negative Pressure Wound Therapy ◽  
Skin Wound ◽  
Low Temperature Plasma ◽  
Wound Therapy ◽  
Skin Wound Healing ◽  
Temperature Plasma ◽  
Marrow Mesenchymal Stem Cells

Low-temperature plasma (LTP; 3 min/day), negative pressure wound therapy (NPWT; 4 h/day), and bone marrow mesenchymal stem cells (MSCs; 1 × 106 cells/day) were used as mono- and combination therapy in an acute excisional skin wound-healing ICR mouse model. These therapies have been beneficial in treating wounds. We investigated the effectiveness of monotherapy with LTP, NPWT, and MSC and combination therapy with LTP + MSC, LTP + NPWT, NPWT + MSC, and LTP + NPWT + MSC on skin wounds in mice for seven consecutive days. Gene expression, protein expression, and epithelial thickness were analyzed using real time polymerase chain reaction (RT-qPCR), western blotting, and hematoxylin and eosin staining (H&E), respectively. Wound closure was also evaluated. Wound closure was significantly accelerated in monotherapy groups, whereas more accelerated in combination therapy groups. Tumor necrosis factor-α (TNF-α) expression was increased in the LTP monotherapy group but decreased in the NPWT, MSC, and combination therapy groups. Expressions of vascular endothelial growth factor (VEGF), α-smooth muscle actin (α-SMA), and type I collagen were increased in the combination therapy groups. Re-epithelialization was also considerably accelerated in combination therapy groups. Our findings suggest that combination therapy with LPT, NPWT, and MSC exert a synergistic effect on wound healing, representing a promising strategy for the treatment of acute wounds.

scholarly journals Gypenoside LXXV Promotes Cutaneous Wound Healing In Vivo by Enhancing Connective Tissue Growth Factor Levels Via the Glucocorticoid Receptor Pathway

Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1595 ◽  
Author(s):  
Sungjoo Park ◽  
Eunsu Ko ◽  
Jun Hyoung Lee ◽  
Yoseb Song ◽  
Chang-Hao Cui ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Connective Tissue ◽  
Wound Closure ◽  
Tissue Growth ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound ◽  
And Migration ◽  
Proliferation And Migration

Cutaneous wound healing is a well-orchestrated event in which many types of cells and growth factors are involved in restoring the barrier function of skin. In order to identify whether ginsenosides, the main active components of Panax ginseng, promote wound healing, the proliferation and migration activities of 15 different ginsenosides were tested by MTT assay and scratched wound closure assay. Among ginsenosides, gypenoside LXXV (G75) showed the most potent wound healing effects. Thus, this study aimed to investigate the effects of G75 on wound healing in vivo and characterize associated molecular changes. G75 significantly increased proliferation and migration of keratinocytes and fibroblasts, and promoted wound closure in an excision wound mouse model compared with madecassoside (MA), which has been used to treat wounds. Additionally, RNA sequencing data revealed G75-mediated significant upregulation of connective tissue growth factor (CTGF), which is known to be produced via the glucocorticoid receptor (GR) pathway. Consistently, the increase in production of CTGF was confirmed by western blot and ELISA. In addition, GR-competitive binding assay and GR translocation assay results demonstrated that G75 can be bound to GR and translocated into the nucleus. These results demonstrated that G75 is a newly identified effective component in wound healing.

scholarly journals SOCS3 Negatively Regulates the gp130–STAT3 Pathway in Mouse Skin Wound Healing

2008 ◽  
Vol 128 (7) ◽  
pp. 1821-1829 ◽  
Author(s):  
Bing-Mei Zhu ◽  
Yuko Ishida ◽  
Gertraud W. Robinson ◽  
Margit Pacher-Zavisin ◽  
Akihiko Yoshimura ◽  
...  
Keyword(s):  
Wound Healing ◽  
Mouse Skin ◽  
Skin Wound ◽  
Skin Wound Healing ◽  
Stat3 Pathway

scholarly journals The Phytochemical Shikonin Stimulates Epithelial-Mesenchymal Transition (EMT) in Skin Wound Healing

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Shu-Yi Yin ◽  
An-Ping Peng ◽  
Li-Ting Huang ◽  
Ya-Ting Wang ◽  
Chun-Wen Lan ◽  
...  
Keyword(s):  
Wound Healing ◽  
Topical Treatment ◽  
Immune Modulation ◽  
Epithelial Mesenchymal Transition ◽  
Mouse Skin ◽  
Molecular Data ◽  
Skin Wound ◽  
Skin Wound Healing ◽  
Mesenchymal Transition

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.

scholarly journals Wound healing revised: A novel reepithelialization mechanism revealed by in vitro and in silico models

2013 ◽  
Vol 203 (4) ◽  
pp. 691-709 ◽  
Author(s):  
Kai Safferling ◽  
Thomas Sütterlin ◽  
Kathi Westphal ◽  
Claudia Ernst ◽  
Kai Breuhahn ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Closure ◽  
Time Lag ◽  
Immunohistochemical Analysis ◽  
Surrounding Tissue ◽  
Final Destination ◽  
Large Numbers ◽  
And Migration ◽  
In Silico Models

Wound healing is a complex process in which a tissue’s individual cells have to be orchestrated in an efficient and robust way. We integrated multiplex protein analysis, immunohistochemical analysis, and whole-slide imaging into a novel medium-throughput platform for quantitatively capturing proliferation, differentiation, and migration in large numbers of organotypic skin cultures comprising epidermis and dermis. Using fluorescent time-lag staining, we were able to infer source and final destination of keratinocytes in the healing epidermis. This resulted in a novel extending shield reepithelialization mechanism, which we confirmed by computational multicellular modeling and perturbation of tongue extension. This work provides a consistent experimental and theoretical model for epidermal wound closure in 3D, negating the previously proposed concepts of epidermal tongue extension and highlighting the so far underestimated role of the surrounding tissue. Based on our findings, epidermal wound closure is a process in which cell behavior is orchestrated by a higher level of tissue control that 2D monolayer assays are not able to capture.

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