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HMGB1 promotes hair growth via the modulation of prostaglandin metabolism.

ABSTRACT: Unexpected hair growth can occur after tissue injury. The pathogenic mechanism for this phenomenon is unknown but is likely related to inflammatory mediators. One such mediator is high-mobility group box 1 (HMGB1), a ubiquitous nuclear protein that is released from cell nuclei after tissue damage. To elucidate the effect of HMGB1 on hair growth and understand its mechanism of action, we evaluated the effect of HMGB1 treatment on hair shaft elongation and on mRNA and protein expression in cultured human dermal papilla cells (hDPCs). HMGB1 enhanced hair shaft elongation in an ex vivo hair organ culture. In hDPCs, HMGB1 treatment significantly increased mRNA and protein expression levels of prostagladin E synthases. HMGB1 also stimulated prostaglandin E2 (PGE₂) secretion from hDPCs. Finally, blocking the receptor for advanced glycation end-products, a canonical HMGB1 receptor, inhibited HMGB1-induced PGE₂ production and hair shaft elongation. Our results suggest that HMGB1 promotes hair growth via PGE₂ secretion from hDPCs. This mechanism can explain the paradoxical phenomenon of trauma-induced hair growth. Thus, HGMB1 can be a viable therapeutic target for the treatment of alopecia.

SUBMITTER: Hwang JH

PROVIDER: S-EPMC6491442 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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HMGB1 promotes hair growth via the modulation of prostaglandin metabolism.

Hwang Ji-Hye JH Chu Howard H Ahn Yuri Y Kim Jino J Kim Do-Young DY

Scientific reports 20190430 1

Unexpected hair growth can occur after tissue injury. The pathogenic mechanism for this phenomenon is unknown but is likely related to inflammatory mediators. One such mediator is high-mobility group box 1 (HMGB1), a ubiquitous nuclear protein that is released from cell nuclei after tissue damage. To elucidate the effect of HMGB1 on hair growth and understand its mechanism of action, we evaluated the effect of HMGB1 treatment on hair shaft elongation and on mRNA and protein expression in culture ...[more]

PMID: 31040377

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Project description:Black soldier fly (BSF), Hermetia illucens (L.) (Diptera: Stratiomyidae), is a promising bio-agent to transform organic wastes into valuable insect biomass, and the intestinal microbes play an essential role in this process. Here, we report that Citrobacter amalonaticus, a Gram-negative gut commensal bacterium of BSF larvae, can colonize the whole intestines of the larva and significantly promote the larval growth and development. The bacterial association with the larva had a marked impact on the larval transcriptome and modulated the expression of genes involved in dozens of biological pathways including host macro-nutrient metabolism and immune response. We investigated the underlying mechanisms driving the interaction and found that C. amalonaticus association can directly promote the expression of two gene families related to intestinal protein metabolism: Hitryp serine protease trypsin family and Himtp metallopeptidase family. To determine the gene function, we developed a symbiont-mediated double-strand RNA interference approach and successfully achieved gene knockdown in larval midgut in situ. Knockdown of the two gene families and protease inhibition in larval intestines attenuated the promoting effects on larval growth significantly. The results indicate that the gut symbiont promotes BSF larval growth partly via modulating the expression of the genes involved in intestinal protein metabolism. Taken together, this study establishes a novel genetic tool to study the insect functional genomics and the host-symbiont interaction and sheds light on the important roles of intestinal protein metabolism on the interaction. IMPORTANCE Black solider fly larvae and the gut microbiota can recycle nutrients from various organic wastes into valuable insect biomass. We found that Citrobacter amalonaticus, a gut commensal bacterium of the insect, exerts beneficial effects on larval growth and development and that the expression of many metabolic larval genes was significantly impacted by the symbiont. To identify the larval genes involved in the host-symbiont interaction, we engineered the symbiont to produce double-strand RNA and enabled the strain to silence host genes in the larval gut environment where the interaction takes place. With this approach, we confirmed that two intestinal protease families are involved in the interaction and provided further evidence that intestinal protein metabolism plays a role in the interaction. This work expands the genetic toolkits available to study the insect functional genomics and host-symbiont interaction and provide the prospective for the future application of gut microbiota on the large-scale bioconversion.

Project description:BackgroundAlopecia affects millions of individuals globally, with hair loss becoming more common among young people. Various traditional Chinese medicines (TCM) have been used clinically for treating alopecia, however, the effective compounds and underlying mechanism are less known. We sought to investigate the effect of Alpinetin (AP), a compound extracted from Fabaceae and Zingiberaceae herbs, in hair regeneration.MethodsAnimal model for hair regeneration was mimicked by depilation in C57BL/6J mice. The mice were then topically treated with 3 mg/ml AP, minoxidil as positive control (PC), or solvent ethanol as vehicle control (VC) on the dorsal skin. Skin color changes which reflected the hair growth stages were monitored and pictured, along with H&E staining and hair shaft length measurement. RNA-seq analysis combined with immunofluorescence staining and qPCR analysis were used for mechanism study. Meanwhile, Gli1CreERT2; R26RtdTomato and Lgr5EGFP-CreERT2; R26RtdTomato transgenic mice were used to monitor the activation and proliferation of Gli1+ and Lgr5+ HFSCs after treatment. Furthermore, the toxicity of AP was tested in keratinocytes and fibroblasts from both human and mouse skin to assess the safety.ResultsWhen compared to minoxidil-treated and vehicle-treated control mice, topical application of AP promoted anagen initiation and delayed catagen entry, resulting in a longer anagen phase and hair shaft length. Mechanistically, RNA-seq analysis combined with immunofluorescence staining of Lef1 suggested that Lgr5+ HFSCs in lower bulge were activated by AP via Wnt signaling. Other HFSCs, including K15+, Lef1+, and Gli1+ cells, were also promoted into proliferating upon AP treatment. In addition, AP inhibited cleaved caspase 3-dependent apoptosis at the late anagen stage to postpone regression of hair follicles. More importantly, AP showed no cytotoxicity in keratinocytes and fibroblasts from both human and mouse skin.ConclusionThis study clarified the effect of AP in promoting hair regeneration by activating HFSCs via Wnt signaling. Our findings may contribute to the development of a new generation of pilatory that is more efficient and less cytotoxic for treating alopecia.

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HMGB1 promotes hair growth via the modulation of prostaglandin metabolism.

Publications

HMGB1 promotes hair growth via the modulation of prostaglandin metabolism.

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