Critical in vivo roles of WNT10A in wound healing by regulating collagen expression/synthesis in WNT10A-deficient mice

Wang, Ke-Yong; Yamada, Sohsuke; Izumi, Hiroto; Tsukamoto, Manabu; Nakashima, Tamiji; Tasaki, Takashi; Guo, Xin; Uramoto, Hidetaka; Sasaguri, Yasuyuki; Kohno, Kimitoshi

doi:10.1371/journal.pone.0195156

Cited by 21 publications

(26 citation statements)

References 38 publications

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“…WNT10A also plays an important role in cancer. Its absence can delay the healing of dorsal skin wounds in mice [ 57 ], while tumors are considered as “unhealable” wounds. Related to the mechanism of WNT10A in skin wound healing, its absence can inhibit the expression of collagen, thereby preventing tumor occurrence [ 58 ].…”

Section: Discussion and Summarymentioning

confidence: 99%

Using WGCNA (weighted gene co-expression network analysis) to identify the hub genes of skin hair follicle development in fetus stage of Inner Mongolia cashmere goat

Hai

et al. 2020

PLoS ONE

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Objective Mature hair follicles represent an important stage of hair follicle development, which determines the stability of hair follicle structure and its ability to enter the hair cycle. Here, we used weighted gene co-expression network analysis (WGCNA) to identify hub genes of mature skin and hair follicles in Inner Mongolian cashmere goats. Methods We used transcriptome sequencing data for the skin of Inner Mongolian cashmere goats from fetal days 45–135 days, and divided the co expressed genes into different modules by WGCNA. Characteristic values were used to screen out modules that were highly expressed in mature skin follicles. Module hub genes were then selected based on the correlation coefficients between the gene and module eigenvalue, gene connectivity, and Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The results were confirmed by quantitative polymerase chain reaction (qPCR). Results Ten modules were successfully defined, of which one, with a total of 3166 genes, was selected as a specific module through sample and gene expression pattern analyses. A total of 584 candidate hub genes in the module were screened by the correlation coefficients between the genes and module eigenvalue and gene connectivity. Finally, GO/KEGG functional enrichment analyses detected WNT10A as a key gene in the development and maturation of skin hair follicles in fetal Inner Mongolian cashmere goats. qPCR showed that the expression trends of 13 genes from seven fetal skin samples were consistent with the sequencing results, indicating that the sequencing results were reliable.n

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Section: Discussion and Summarymentioning

confidence: 99%

Using WGCNA (weighted gene co-expression network analysis) to identify the hub genes of skin hair follicle development in fetus stage of Inner Mongolia cashmere goat

Hai

et al. 2020

PLoS ONE

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“…However, Wnt10a expression was down-regulated in MDSPCs by MRL/MpJ serum. Recently, it was reported that Wnt10 2/2 mice have delayed wound healing in a skin-injury model (33). Next, we asked whether MRL/ MpJ serum has a similar effect on aged MDSPCs.…”

Section: Circulating Serum Factors From Mrl/mpj Mice Regulate Functiomentioning

confidence: 97%

Hypoxia‐inducible factor 1α (HIF‐1α) is a major determinant in the enhanced function of muscle‐derived progenitors from MRL/MpJ mice

et al. 2019

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Although the mouse strain Murphy Roths Large (MRL/MpJ) possesses high regenerative potential, the mechanism of tissue regeneration, including skeletal muscle, in MRL/MpJ mice after injury is still unclear. Our previous studies have shown that muscle‐derived stem/progenitor cell (MDSPC) function is significantly enhanced in MRL/MpJ mice when compared with MDSPCs isolated from age‐matched wild‐type (WT) mice. Using mass spectrometry–based proteomic analysis, we identified increased expression of hypoxia‐inducible factor (HIF) 1α target genes (expression of glycolytic factors and antioxidants) in sera from MRL/MpJ mice compared with WT mice. Therefore, we hypothesized that HIF‐1α promotes the high muscle healing capacity of MRL/MpJ mice by increasing the potency of MDSPCs. We demonstrated that treating MRL/MpJ MDSPCs with dimethyloxalylglycine and CoCl2 increased the expression of HIF‐1α and target genes, including angiogenic and cell survival genes. We also observed that HIF‐1α activated the expression of paired box (Pax)7 through direct interaction with the Pax7 promoter. Furthermore, we also observed a higher myogenic potential of MDSPCs derived from prolyl hydroxylase (Phd) 3—knockout (Phd3−/−) mice, which displayed higher stability of HIF‐1α. Taken together, our findings suggest that HIF‐1α is a major determinant in the increased MDSPC function of MRL/MpJ mice through enhancement of cell survival, proliferation, and myogenic differentiation.—Sinha, K. M., Tseng, C., Guo, P., Lu, A., Pan, H., Gao, X., Andrews, R., Eltzschig, H., Huard, J. Hypoxia‐inducible factor 1α (HIF‐1α) is a major determinant in the enhanced function of muscle‐derived progenitors from MRL/MpJ mice. FASEB J. 33, 8321–8334 (2019). http://www.fasebj.org

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“…This suggests that TGFβ1 serves an activator for fibroblast proliferation and ECM production, whereas TGFβ3 works as an inhibitor of ECM production. Signalling factors belonging to canonical WNT and PDGF pathways also regulate fibroblast activity and can serve the role of activators and inhibitors in the model.…”

Section: Resultsmentioning

confidence: 99%

A multiscale hybrid mathematical model of epidermal‐dermal interactions during skin wound healing

Wang

Guerrero‐Juarez

Qiu

et al. 2019

Experimental Dermatology

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Following injury, skin activates a complex wound healing programme. While cellular and signalling mechanisms of wound repair have been extensively studied, the principles of epidermal‐dermal interactions and their effects on wound healing outcomes are only partially understood. To gain new insight into the effects of epidermal‐dermal interactions, we developed a multiscale, hybrid mathematical model of skin wound healing. The model takes into consideration interactions between epidermis and dermis across the basement membrane via diffusible signals, defined as activator and inhibitor. Simulations revealed that epidermal‐dermal interactions are critical for proper extracellular matrix deposition in the dermis, suggesting these signals may influence how wound scars form. Our model makes several theoretical predictions. First, basal levels of epidermal activator and inhibitor help to maintain dermis in a steady state, whereas their absence results in a raised, scar‐like dermal phenotype. Second, wound‐triggered increase in activator and inhibitor production by basal epidermal cells, coupled with fast re‐epithelialization kinetics, reduces dermal scar size. Third, high‐density fibrin clot leads to a raised, hypertrophic scar phenotype, whereas low‐density fibrin clot leads to a hypotrophic phenotype. Fourth, shallow wounds, compared to deep wounds, result in overall reduced scarring. Taken together, our model predicts the important role of signalling across dermal‐epidermal interface and the effect of fibrin clot density and wound geometry on scar formation. This hybrid modelling approach may be also applicable to other complex tissue systems, enabling the simulation of dynamic processes, otherwise computationally prohibitive with fully discrete models due to a large number of variables.

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Critical in vivo roles of WNT10A in wound healing by regulating collagen expression/synthesis in WNT10A-deficient mice

Cited by 21 publications

References 38 publications

Using WGCNA (weighted gene co-expression network analysis) to identify the hub genes of skin hair follicle development in fetus stage of Inner Mongolia cashmere goat

Using WGCNA (weighted gene co-expression network analysis) to identify the hub genes of skin hair follicle development in fetus stage of Inner Mongolia cashmere goat

Hypoxia‐inducible factor 1α (HIF‐1α) is a major determinant in the enhanced function of muscle‐derived progenitors from MRL/MpJ mice

A multiscale hybrid mathematical model of epidermal‐dermal interactions during skin wound healing

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