BackgroundThe key pathophysiological changes in androgenetic alopecia (AGA) are limited to hair follicles (HFs) in frontal and vertex regions, sparing the occipital region. Objectives To identify biological differences among HF subpopulations. Methods Paired vertex and occipital HFs from 10 male donors with AGA were collected for RNA sequencing assay. Furthermore, HF and cell experiments were conducted on the identified key genes to reveal their roles in AGA. Results Transcriptome profiles revealed that 506 mRNAs, 55 microRNAs and 127 long noncoding RNAs were differentially expressed in the AGA vertex HFs. Pathway analysis of mRNAs and microRNAs revealed involvement of the hypoxiainducible factor (HIF)-1, Wnt/β-catenin, and focal adhesion pathways. Differential expression of HIF-1 prolyl hydroxylase enzymes (EGLN1, EGLN3) and Wnt/βcatenin pathway inhibitors (SERPINF1, SFRP2) was experimentally validated. In vitro studies revealed that reduction of EGLN1, EGLN3, SERPINF1 and SFRP2 stimulated proliferation of dermal papilla cells. Ex vivo HF studies showed that downregulation of EGLN1, EGLN3 and SERPINF1 promoted HF growth, postponed HF catagen transition, and prolonged the anagen stage, suggesting that these genes may be potentially utilized as therapeutic targets for AGA. Conclusions We characterized key transcriptome changes in male AGA HFs, and found that HIF-1 pathway-related genes (EGLN1, EGLN3) and Wnt pathway inhibitors (SERPINF1, SFRP2) may play important roles in AGA.What is already known about this topic?• Multiple differentially expressed genes and signalling pathways have been found between hair follicles (HFs) in the balding area (frontal and vertex regions) and nonbalding area (occipital region) of individuals with androgenetic alopecia (AGA). • A whole-transcriptome atlas of the vertex and occipital region is lacking.
Background: Oxidative damage has been found in various types of hair loss. As a polyphenolic phytoalexin, resveratrol (RSV) is known as an antioxidant, anti-inflammatory and anti-apoptotic agent.Objective: Thus, we aim to examine the effects of RSV on hair growth. Methods: In vivo C57BL/6 mice were used to evaluate the effects of RSV on hair cycle, hair length, skin thickness, hair follicle diameter, hair cycle score and the percentage of hair cycle stage. Then hair shaft length and hair cycle were evaluated by human hair follicles (HFs) ex vivo. The proliferative activities of human dermal papilla cells (hDPCs) cultured in vitro with RSV were assessed using RTCA. The ability of RSV to protect hDPCs against H 2 O 2 -induced oxidative damage is examined by a ROS assay kit. Results: Topical application of RSV significantly promoted hair growth and stimulated the transition of hair cycle from telogen into the anagen phase on shaved C57BL/6 mice. Ex vivo experiments showed that RSV increased the hair shaft length of HFs and delayed the entry into catagen. In vitro experiments indicated that RSV proliferated hDPCs and prevented hDPCs from oxidative damage caused by H 2 O 2 . Conclusion: RSV can promote hair growth and may be a potential candidate for the treatment of hair loss.
Hair follicles (HFs) play an essential role in sustaining a persistent hair growth cycle. The activities of dermal papilla cells (DPCs) and other cells inside the HFs dominate the process of hair growth. However, the detailed molecular mechanisms remain largely unknown. To investigate the role of citric acid (CA) metabolism in hair growth, we evaluated the effect of citrate synthase (CS)-CA axis on hair growth in vivo and in vitro. Mice hair growth was evaluated by morphology and histopathology analysis. The inflammation and apoptosis levels in mice, HFs, and DPCs were detected by immunohistofluorescence, qPCR, ELISA, western blot, and TUNEL assay. Cell proliferation, cell cycle, and cell apoptosis in DPCs were analyzed by real-time cell analysis and flow cytometer. We found that subcutaneous injection of CA in mice caused significant hair growth suppression, skin lesion, inflammatory response, cell apoptosis, and promotion of catagen entry, compared with the saline control, by activating p-p65 and apoptosis signaling in an NLRP3-dependent manner. In cultured human HFs, CA attenuated the hair shaft production and accelerated HF catagen entry by regulating the above-mentioned pathways. Additionally, CA hampered the proliferation rate of DPCs via inducing cell apoptosis and cell cycle arrest. Considering that citrate synthase (CS) is responsible for CA production and is a rate-limiting enzyme of the tricarboxylic acid cycle, we also investigated the role of CS in CA metabolism and hair growth. As expected, knockdown of CS reduced CA production and reversed CA-induced hair growth inhibition, anagen shrink, inflammation, and apoptosis both in HFs and DPCs.Our experiments demonstrated that CS-CA axis serves as an important mediator and might be a potential therapeutic target in hair growth.
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