Expression of matrix metalloproteinases and tissue inhibitor of matrix metalloproteinases in the hair cycle

Hou, Chun‐Han; Miao, Yong; Wang, Xue; Chen, Chaoyue; Lin, Bojie; Hu, Zhiqi

doi:10.3892/etm.2016.3319

Cited by 25 publications

(18 citation statements)

References 36 publications

(33 reference statements)

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“…We also noted that highly efficient ablation of TGFβ occurs following topical application to 6 week old mice with another peak at 10 weeks. This timing is similar to the mouse hair anagen cycle [35]. It is possible that topical tamoxifen targeting genes in KC may have heightened efficiency during anagen.…”

Section: Discussionmentioning

confidence: 52%

Keratinocyte-derived TGFβ is not required to maintain skin immune homeostasis

Yang

Zenke

Hirai

et al. 2019

Journal of Dermatological Science

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Background: Transforming growth factor beta 1 (TGFβ) is known to be a regulator of autoimmunity. Loss of TGFβ leads to severe multi-organ autoimmunity in mice. In skin, role of TGFβ in suppressing autoimmunity is unclear. Objective: Determine whether Keratinocyte (KC)-derived TGFβ is required for skin immune homeostasis. Methods: We generated K14-CreER T2 TGFβ1 fl/fl (TGFβ DKC) mice allowing for tamoxifen-induced deletion of TGFβ1 in KC. The phenotype of skin was analyzed and compared to mice in which epidermal activation of TGFβ is impaired. Results: KC was the major source of TGFβ in epidermis. Topical tamoxifen application led to efficient TGFβ1 deletion. The expected acanthosis was observed but no inflammatory infiltrate or altered numbers of resident immune cells were evident. Similarly, Itgb6 À/À x K14Cre Itgb8 f/f (Itgb6 À/À Itgb8 DKC) mice lacking both epidermal TGFβ-activating integrins showed no evidence of cutaneous inflammation. Conclusions: KC-derived TGFβ and epidermal TGFβ activation are not required to suppress skin autoimmunity in steady state.

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Section: Discussionmentioning

confidence: 52%

Keratinocyte-derived TGFβ is not required to maintain skin immune homeostasis

Yang

Zenke

Hirai

et al. 2019

Journal of Dermatological Science

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“…Histological analysis (Fontana-Masson staining) of the back skin of 5-week old mice, revealed that similarly to KIT +/+ control mice, the hair follicles of both KIT Dup/+ and KIT D17/+ mice are long and the dermal papilla in the hair bulb is completely coated by the matrix, the keratogenous zone region is clearly visible and is connected to the hair shaft and dermal papilla, and fibrous tract is substantially invisible in the skin (Figure 2). These results indicate that similar to the KIT +/+ control mice, the hair follicles of 5-week-old KIT Dup/+ and KIT D17/+ mice are in the growing stage (anagen V or VI), which is advantageous for observations of hair follicle shape, and melanin distribution since melanin synthesis is more active during this stage (Hou et al, 2016). The hair follicle shape implies that both the splice mutation and CDS duplication mutation did not impair the hair follicle development significantly.…”

Section: The Kit Splice Mutation Significantly Reduces Melanin Accumumentioning

confidence: 53%

Functional Analysis of KIT Gene Structural Mutations Causing the Porcine Dominant White Phenotype Using Genome Edited Mouse Models

Sun

Qin

et al. 2020

Front. Genet.

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The dominant white phenotype in pigs is thought to be mainly due to a structural mutation in the KIT gene, a splice mutation (G > A) at the first base in intron 17 which leads to the deletion of exon 17 in the mature KIT mRNA. However, this hypothesis has not yet been validated by functional studies. Here, we created two mouse models, KIT D17/+ to mimic the splice mutation, and KIT Dup/+ to partially mimic the duplication mutation of KIT gene in dominant white pigs using CRISPR/Cas9 technology. We found that the splice mutation homozygote is lethal and the heterozygous mice have a piebald coat. Slightly increased expression of KIT in KIT Dup/+ mice did not confer the patched phenotype and had no obvious impact on coat color. Interestingly, the combination of these two mutations reduced the phosphorylation of PI3K and MAPK pathway associated proteins, which may be related to the impaired migration of melanoblasts observed during embryonic development that eventually leads to the dominant white phenotype.

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“…2). These results indicate that similar to the KIT +/+ control mice, the hair follicles of 5-week-old KIT Dup/+ and KIT D17/+ mice are in the growing stage (anagen V or VI), which is advantageous for the observation of the hair follicle shape, and melanin distribution due to melanin synthesis is more active during this stage [15]. The results of hair follicle shape imply that both the splice mutation and duplication mutation did not impair the hair follicle development significantly.…”

Section: Resultsmentioning

confidence: 86%

Functional analysis of KIT gene structural mutations causing porcine dominant white phenotype by using genome edited mouse models

Sun

Qin

et al. 2019

Preprint

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24Dominant white phenotype in pigs is considered to be caused by two structural 25 mutations in KIT gene, including a 450-kb duplication encompassing the entire KIT 26 gene, and a splice mutation (G > A) at the first base in intron 17, which leads to the 27 deletion of exon 17 in mature KIT mRNA, and the production of KIT protein lacking a 28 critical catalytic domain of kinase. However, this speculation has not yet been validated 29 by functional studies. Here, by using CRISPR/Cas9 technology, we created two mouse 30 models mimicing the structural mutations of KIT gene in dominant white pigs, 31 including the splice mutation mouse model KIT D17/+ with exon 17 of one allele of KIT 32 gene deleted, and duplication mutation mouse model KIT Dup/+ with one allele of KIT 33 gene coding sequence (CDS) duplicated. We found that each mutation individually can 34 not cause dominant white phenotype. Splice mutation homozygote is lethal and 35 heterozygous mice present piebald coat. Inconsistent with previous speculation, we 36 found KIT gene duplication mutation did not confer the patched phenotype, and had no 37 obvious impact on coat color. Interestingly, combination of these two mutations lead to 38 dominant white phenotype. Further molecular analysis revealed that combination of 39 these two structural mutations could inhibit the kinase activity of the KIT protein, thus 40 reduce the phosphorylation level of PI3K and MAPK pathway associated proteins, 41 which may be related to the observed impaired migration of melanoblasts during 42 embryonic development, and eventually lead to dominant white phenotype. Our study 43 provides a further insight into the underlying genetic mechanisms of porcine dominant 44 white coat colour.45Author summary 46 KIT plays a critical role in control of coat colour in mammals. Two mutation 47 coexistence in KIT are considered to be the cause of the Dominant white phenotype in 48 pigs. One mutation is a 450-kb large duplication encompassing the entire KIT gene, 49 another mutation is a splice mutation causing the skipping of KIT exon 17. The 50 mechanism of these two mutations of KIT on coat color formation has not yet been 51 validated. In this study, by using genome edited mouse models, we found each 52 structural mutation individual does not lead dominant white phenotype, but 53 combination of these two mutations could lead to a nearly complete white coat colour 54 similar to pig dominant white phenotype, possibly due to the inhibition of the kinase 55 activity of the KIT protein, thus its signalling function on PI3K and MAPK pathways, 56 leading to impaired migration of melanoblasts during embryonic development, and 57 eventually lead to dominant white phenotype. Our study provides a further insight into 58 the underlying genetic mechanisms of porcine dominant white coat colour. 59 60 Introduction 61 Due to domestication and long term selection, dominant white is a widespread coat 62 color among domestic pig breeds, such as Landrace and Large White [1]. The dominant 63 white phen...

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Expression of matrix metalloproteinases and tissue inhibitor of matrix metalloproteinases in the hair cycle

Cited by 25 publications

References 36 publications

Keratinocyte-derived TGFβ is not required to maintain skin immune homeostasis

Keratinocyte-derived TGFβ is not required to maintain skin immune homeostasis

Functional Analysis of KIT Gene Structural Mutations Causing the Porcine Dominant White Phenotype Using Genome Edited Mouse Models

Functional analysis of KIT gene structural mutations causing porcine dominant white phenotype by using genome edited mouse models

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