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Kokabu, S.

Publications and source records attributed to Kokabu, S..

4 recordsLinked to original sources

Sex Differences in Physiological Hair Cycling and Adhesive Material-Induced Hair Regeneration in Mice

Sex differences in hair growth are clinically evident, but sex-dependent regulation of physiological hair cycling and injury-induced hair regeneration remains incompletely understood. We compared physiological dorsal hair-cycle progression and adhesive material-induced localized hair regeneration in male and female C3H/He mice. Males entered the second and third anagen phases earlier than females, indicating longer telogen phases in females. In contrast, localized hair regrowth after application and removal of a cyanoacrylate adhesive material appeared earlier in females. Ovariectomy induced widespread telogen-to-anagen transition and therefore did not permit isolation of ovarian-hormone effects on the localized response. RNA sequencing of intact dorsal skin identified sex-dependent baseline expression profiles involving inflammation, wound response, and tissue repair. Independent time-course quantitative PCR further demonstrated sex-dependent expression of inflammatory and reparative genes after adhesive material application. Local clodronate liposome administration alone induced delayed perifocal hair growth. When combined with adhesive material application, clodronate treatment markedly delayed wound healing and localized hair regrowth in males, whereas these responses were comparatively preserved in females. These findings show that physiological hair cycling and adhesive material-induced hair regeneration exhibit distinct sex differences and suggest that the localized regenerative response is more macrophage-dependent in males than in females.

developmental biology↗

Regional Differences in Dorsal Skin Determine the Rate of Adhesive Material-Induced Hair Regeneration

Dorsal skin is widely used in mouse wound-healing, dermatitis, and hair-cycle models, but is often treated as a uniform site. We investigated whether adhesive material (cyanoacrylate)-induced hair regeneration, a model we previously reported, differs by position within the dorsal skin. Adhesive material was applied to four regions along the cranial-to-caudal axis of the mouse dorsal skin. Hair regrowth appeared earlier at the cranial sites than at the caudal sites, and this difference persisted through late anagen and the anagen-to-catagen transition. In contrast, hair regrowth after full-thickness skin excision was slower, smaller in area, and less reproducible than that after adhesive material application. Expression of Hox genes, including Hoxa9, Hoxb9, Hoxc9, Hoxa10, and Hoxc10, was higher at the caudal sites than at the cranial sites but did not correlate with the timing of hair regrowth. RNA sequencing of intact skin from the cranial and caudal sites revealed distinct baseline profiles, including differences in the Wnt inhibitor Sfrp4 and the adipogenic genes Ppar{gamma} and Fabp4. Early after adhesive material application, histological changes and the expression of inflammation- and tissue-repair-related genes also differed between the cranial and caudal skin. These findings indicate that mouse dorsal skin is not a uniform experimental field and that cranial-to-caudal position should be considered when designing and interpreting hair-regeneration and wound-healing experiments in mice.

developmental biology↗

BMP-3b suppresses proliferation, migration, invasion, and TGF-β 1/Smad3 signaling in breast cancer cells

ObjectiveBone morphogenetic protein-3b (BMP-3b), also known as growth differentiation factor 10, has been implicated in tumor suppression; however, its role in breast cancer and its interaction with transforming growth factor-{beta}1 (TGF-{beta}1) signaling remain incompletely understood. MethodsPublicly available datasets were used to examine BMP-3b expression in breast lesions and its association with overall survival in patients with stage III or IV breast cancer. Human MCF-7 and murine 4T1 breast cancer cells were treated with recombinant BMP-3b. Cell proliferation, migration, invasion, epithelial-mesenchymal transition-related proteins, and TGF-{beta}1-induced Smad3 phosphorylation were assessed using Cell Counting Kit-8, scratch wound-healing, Transwell invasion, and Western blot assays. ResultsBMP-3b expression was lower in ductal carcinoma in situ than in normal mammary tissue. Low BMP-3b expression was associated with poorer overall survival in patients with stage III or IV breast cancer. BMP-3b reduced proliferation of MCF-7 and 4T1 cells and inhibited migration and invasion of 4T1 cells. BMP-3b increased E-cadherin and decreased vimentin expression in both cell lines. It also attenuated TGF-{beta}1-induced migration, invasion, and Smad3 phosphorylation in 4T1 cells. ConclusionsBMP-3b suppresses malignant phenotypes of breast cancer cells and modulates TGF- {beta}1/Smad3 signaling. These findings identify BMP-3b as a potential endogenous regulator of breast cancer progression.

cell biology↗

Wound-initiated hair regeneration by adhesive and shrinkable materials

Although there is a global demand for hair regrowth, particularly among middle-aged and older individuals, an effective hair growth technology has not yet been established1. Hair follicle neogenesis is restricted to the embryonic period, but hair regeneration accompanied by wound healing has been observed under some conditions2-4; however, the underlying mechanisms are unclear. Herein, we demonstrated that creating a wound without dermal defects effectively induced postneonatal hair follicle neogenesis. Separating the epidermis from the dermis by topical application of adhesive and shrinkable materials to mouse skin promoted epidermal regeneration, followed by new hair follicle formation. Hair follicle regeneration, accompanied by the upregulation of related genes, can be induced in mice, including middle-aged and aged mice, regardless of species, sex, skin location, or age. The cycle of the regenerated hair eventually synchronized with that of the surrounding physiological hairs. Our new hair regeneration technique based on reproduction of epidermis-dermis interactions provides a novel means to treat hair loss, including androgenetic alopecia.

cell biology↗