Background: The goal of the present studies was to localize two proteins known to be involved in regulation of cell proliferation and survival in specific cell populations in normal SENCAR mouse skin and during multi-stage skin carcinogenesis. The proteins evaluated included activated Akt, as defined by phosphorylation of Akt at Serine-473 (pAkt) and mammalian target of rapamycin (pmTOR), defined by phosphorylation of mTOR at Serine-2448 (pmTOR). The cell populations examined included mouse keratinocyte stem cells (KSCs) within hair follicles and preneoplastic papilloma cells.
Materials And Methods: Immunochemical staining analysis as well as triple color immunofluorescence in combination with confocal microscopy were used to evaluate the presence of activated Akt and mammalian target of rapamycin (mTOR) in KSCs within the bulge niche of hair follicles, as identified by expression of the specific markers of mouse KSCs, CD34 and cytokeratin 15 (K15). Western blot analysis was used to examine CD34 and K15 protein levels in dorsal skin isolated from SENCAR mice during multi-stage skin carcinogenesis.
Results: CD34+/K15+ KSCs were located only in the outer root sheath (ORS) of a specific niche within hair follicles defined as "the bulge". The location of CD34+/K15+ KSCs remained restricted to the bulge region throughout the 22-week time-period examined during which pre-malignant papillomas developed and rapidly expanded. There was a significant decrease in K15 protein levels at 24 h and 15 weeks in dorsal skin treated with DMBA/TPA compared to CD34 protein levels. CD34+ cells within the numerous hair follicles in hyperplastic skin were found to undergo proliferation during the process of multi-stage skin carcinogenesis based on their staining with antibodies directed against proliferating cell nuclear antigen (PCNA). While pAkt was present within the bulge region of hair follicles, pmTOR was present in cells in the ORS of the bulge region as well as the upper infundibulum of hair follicles in dorsal skin treated with acetone. Within papillomas tissues isolated at 15 weeks following DMBA/TPA treatment, pAkt was localized to suprabasal cells with nominal staining of pAkt in the basal cell layer. There were fewer cells within the basal cell layer that contained pmTOR, in addition to the presence of pmTOR in suprabasal cells within papillomas.
Conclusion: These results provide first time evidence for pAkt and pmTOR in CD34+/K15+ KSCs localized to the outer root sheath niche of the bulge region of mouse hair follicles. Taken together, the present observations suggest that pAkt and pmTOR may allow this cell population to evade terminal differentiation and to persist for long periods of time in their specific niche. Strategies that target pAkt and pmTOR may deplete both cells within the CD34+/K]5+ KSCs compartment, as well as impacting the survival of nonproliferating suprabasal cells within pre-malignant papillomas.
Download full-text PDF |
Source |
---|
Front Surg
December 2024
Academic Vascular Surgical Unit, Hull University Teaching Hospitals NHS Trust, Hull, United Kingdom.
Background: Surgical site infections (SSIs) pose a significant challenge to healthcare systems by elevating patient morbidity and mortality and driving up financial costs. Preoperative skin preparation is crucial for preventing SSIs; however, certain traditional methods of hair removal have been found to increase the risk of SSI development. Mechanical epilation and waxing constitute two relatively explored methods of hair removal, which may hold potential to accelerate wound healing due to the activation of stem cells within hair follicles.
View Article and Find Full Text PDFCureus
November 2024
Department of Surgery, Ng Teng Fong General Hospital, Singapore, SGP.
Trichilemmal cysts, also known as pilar cysts, are commonly found on hair-bearing surfaces, such as the scalp or hairline. These are cysts that form from hair follicles and are benign. We describe an unusual case of a middle-aged lady presenting with a longstanding left-sided inframammary mass that had started growing more in the last year prior to the presentation.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
Nano Drug Delivery Systems (NDDS), Cancer Biology Division, Rajiv Gandhi Centre for Biotechnology, Thycaud P.O, Poojappura, Thiruvananthapuram, Kerala 695014, India. Electronic address:
Severe burns pose significant threats to patient well-being, characterized by pain, inflammation, bacterial infection, and extended recovery periods. While exosome-loaded hydrogels have demonstrated considerable promise in wound healing, current formulations often fall short of achieving optimal therapeutic efficacy for burn wounds due to challenges related to their adaptability to wound shape and limited anti-bacterial capabilities. In this study a novel exosome laden sprayable thermosensitive polysaccharide-based hydrogel (ADA-aPF127@LL18/Exo) comprising alginate dialdehyde (ADA) and aminated Pluronic F127 (aPF127) was fabricated via Schiff base reaction.
View Article and Find Full Text PDFJ Ultrasound Med
December 2024
Department of Dermatology, University of Pisa, Pisa, Italy.
Introduction: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease affecting hair follicles, causing recurrent abscesses and nodules in intertriginous regions. The International HS Severity Score System (IHS4) is widely used to assess HS severity by counting inflammatory nodules, abscesses, and draining fistulas/tunnels. However, traditional clinical examinations may underestimate HS severity due to the presence of subclinical lesions.
View Article and Find Full Text PDFStem Cell Reports
December 2024
Department of Ophthalmology, Tufts Medical Center, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA. Electronic address:
It is widely recognized that the glycocalyx has significant implications in regulating the self-renewal and differentiation of adult stem cells; however, its composition remains poorly understood. Here, we show that the fucose-binding Aleuria aurantia lectin (AAL) binds differentially to basal cells in the stratified epithelium of the human limbus, hair follicle epithelium, and meibomian gland duct. Using fluorescence-activated cell sorting in combination with single-cell transcriptomics, we find that most epithelial progenitor cells and melanocytes in the limbus display low AAL staining (AAL) on their cell surface, an attribute that is gradually lost in epithelial cells as they differentiate into mature corneal cells.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!