Estrogen modulates mesenchymal-epidermal interactions in the adult nipple

Abstract

Maintenance of specialized epidermis requires signals from the underlying mesenchyme; however, the specific pathways involved remain to be identified. By recombining cells from the ventral skin of the K14-PTHrP transgenic mice [which overexpress parathyroid hormone-related protein (PTHrP) in their developing epidermis and mammary glands] with those from wild type, we show that transgenic stroma is sufficient to reprogram wild-type keratinocytes into nipplelike epidermis. To identify candidate nipple-specific signaling factors, we compared gene expression signatures of sorted Pdgfrα-positive ventral K14-PTHrP and wild-type fibroblasts, identifying differentially expressed transcripts that are involved in WNT, HGF, TGFβ, IGF, BMP, FGF and estrogen signaling. Considering that some of the growth factor pathways are targets for estrogen regulation, we examined the upstream role of this hormone in maintaining the nipple. Ablation of estrogen signaling through ovariectomy produced nipples with abnormally thin epidermis, and we identified TGFβ as a negatively regulated target of estrogen signaling. Estrogen treatment represses Tgfβ1 at the transcript and protein levels in K14-PTHrP fibroblasts in vitro, while ovariectomy increases Tgfb1 levels in K14-PTHrP ventral skin. Moreover, ectopic delivery of Tgfβ1 protein into nipple connective tissue reduced epidermal proliferation. Taken together, these results show that specialized nipple epidermis is maintained by estrogen-induced repression of TGFβ signaling in the local fibroblasts.

Characterization of Human Dermal Papilla Cells in Alginate Spheres

“…However, its decreasing rate is consistent even after day 30 in alginate sphere, necessitating other reasons for explanation. If there is little secretory factor from the epithelial component, there is not sufficient proliferative potential in dermal papilla [20,37,38]. We recently reported that factors from the epithelial cells could induce and maintain DPCs' trichogenecity as well as modulate the regulation of DPC gene expression [39].…”

Sox2 in the dermal papilla regulates hair follicle pigmentation

“…As a control, HBSS incubated beads were used. Then, 150 mL of 10 mg/mL of BMP4 cytokine incubated beads suspension was injected using a 12-gauge needle in the top half of the waxed dorsal skin (Treated) while 150 mL of HBSS incubated beads were administered to the bottom (Control) on 3 alternate days according to (Wu et al, 2017). Photo logs were taken to monitor the hair regrow and mice were culled when the control area had fully regrown for hair shaft analysis -5 days after the last injection.…”

Estrogen Receptor Modulators in Viral Infections Such as SARS−CoV−2: Therapeutic Consequences

“…However, this impact is broader and also affects extragenital organs. Interestingly, distinct steps of wound healing, such as epidermal cell proliferation or production of extracellular matrix, are precisely regulated by the timely expression of α/β ΕR [ 84 ]. What is noteworthy is that the benefits of the female sex are diminished in female mammals after menopause, when the production of sex hormones decreases [ 16 ].…”