Pilomatricoma in the infraorbital region.

Key Clinical Message: Pilomatricoma, a rare benign skin tumor arising from hair follicle matrix cells, warrants consideration in the evaluation of subcutaneous nodules or masses, especially when presenting as painless and firm lesions. Accurate diagnosis hinges on histopathological examination, underscoring the significance of clinician vigilance and prompt intervention. Abstract: Pilomatricoma, also referred to as Pilomatrixomas or Calcifying epithelioma of Malherbe, is a rare benign skin tumor derived from hair follicle matrix cells, presents a diagnostic challenge due to its diverse clinical manifestations. Females are more commonly affected by Pilomatricoma. This condition typically manifests as a painless, firm, and slowly progressive lesion. Histopathological analysis shows characteristic findings, such as basaloid cells at the periphery and shadow cells centrally. Immunohistochemical studies assess the expression of cytokeratin's associated with hair matrix differentiation. Complete surgical excision remains the cornerstone of treatment, ensuring favorable outcomes and minimizing the risk of recurrence. Awareness of this entity among clinicians is essential for timely recognition and appropriate intervention. In this specific case-study, we present a case of Pilomatricoma situated in the lower left orbital region of a 32-year-old male individual who had been noticing swelling in that vicinity over the preceding 7 months.

Rational Design of Human Hair Keratin-Driven Proteins for Hair Growth Promotion.

Keratins, the most abundant proteins in human hair, are excellent hair nutrients for growth. However, the complex components of keratin extract hinder their mechanism investigation, and the pure recombinant keratin with poor solubility limited its hair growth promotion efficiency. Here, the water-soluble recombinant keratins (RKs) of K31 and K81 are rationally designed through QTY Code methodology, which are then used to fabricate the microneedles to study the effect of keratin on hair growth. Interestingly, it is discovered that more than 40% of the hair follicles (HFs) in the RK81QTY group entered the anagen on day 12 and the diameter of new hair is 15.10 ± 2.45 µm, which significantly promoted growth and development of HFs and improved new hair quality compared to RK31QTY. Water-soluble RKs significantly enhanced HFs activity and de novo regeneration of robust hairs compared to extract and minoxidil by upregulating the PI3K/AKT/Nf-κB signaling axis. These findings highlight the potential of designing solubilized recombinant keratins with distinct properties to improve therapeutical effects and open new avenues to designing keratin-based proteins.

The Influence of Various Freezing-thawing Methods of Skin on Drug Permeation and Skin Barrier Function.

The selection of skin is crucial for the in vitro permeation test (IVPT). The purpose of this study was to investigate the influence of different freezing-thawing processes on the barrier function of skin and the transdermal permeability of granisetron and lidocaine. Rat and hairless mouse skins were thawed at three different conditions after being frozen at -20℃ for 9 days: thawed at 4℃, room temperature (RT), and 32℃. There were no significant differences in the steady-state fluxes of drugs between fresh and thawed samples, but compared with fresh skin there were significant differences in lag time for the permeation of granisetron in rat skins thawed at RT and 32℃. Histological research and scanning electron microscopy images showed no obvious structural damage on frozen/thawed skin, while immunohistochemical staining and enzyme-linked immunosorbent assay for the tight junction (TJ) protein Cldn-1 showed significantly impaired epidermal barrier. It was concluded that the freezing-thawing process increases the diffusion rate of hydrophilic drugs partly due to the functional degradation of TJs. It's recommended that hairless, inbred strains and identical animal donors should be used, and the selected thawing method of skin should be validated prior to IVPT, especially for hydrophilic drugs.

A biopsy-sized 3D skin model with a perifollicular vascular plexus enables studying immune cell trafficking in the skin.

Human skin vasculature features a unique anatomy in close proximity to the skin appendages and acts as a gatekeeper for constitutive lymphocyte trafficking to the skin. Approximating such structural complexity and functionality in 3D skin models is an outstanding tissue engineering challenge. In this study, we leverage the capabilities of the digital-light-processing bioprinting to generate an anatomically-relevant and miniaturized 3D skin-on-a-chip (3D-SoC) model in the size of a 6 mm punch biopsy. The 3D-SoC contains a perfusable vascular network resembling the superficial vascular plexus of the skin and closely surrounding bioengineered hair follicles. The perfusion capabilities of the 3D-SoC enables the circulation of immune cells, and high-resolution imaging of the immune cell-endothelial cell interactions, namely tethering, rolling, and extravasation in real-time. Moreover, the vascular pattern in 3D-SoC captures the physiological range of shear rates found in cutaneous blood vessels and allows for studying the effect of shear rate on T cell trafficking. In 3D-SoC, as expected,in vitro-polarized T helper 1 (Th1) cells show a stronger attachment on the vasculature compared to naïve T cells. Both naïve and T cells exhibit higher retention in the low-shear zones in the early stages (<5 min) of T cell attachment. Interestingly, at later stages T cell retention rate becomes independent of the shear rate. The attached Th1 cells further transmigrate from the vessel walls to the extracellular space and migrate toward the bioengineered hair follicles and interfollicular epidermis. When the epidermis is not present, Th1 cell migration toward the epidermis is significantly hindered, underscoring the role of epidermal signals on T cell infiltration. Our data validates the capabilities of 3D-SoC model to study the interactions between immune cells and skin vasculature in the context of epidermal signals. The biopsy-sized 3D-SoC model in this study represents a new level of anatomical and cellular complexity, and brings us a step closer to generating a truly functional human skin with its tissue-specific vasculature and appendages in the presence of circulating immune cells.

Efficient Generation of Pancreatic Progenitor Cells from Induced Pluripotent Stem Cells Derived from a Non-Invasive and Accessible Tissue Source-The Plucked Hair Follicle.

The advent of induced pluripotent stem cell (iPSC) technology has brought about transformative advancements in regenerative medicine, offering novel avenues for disease modeling, drug testing, and cell-based therapies. Patient-specific iPSC-based treatments hold the promise of mitigating immune rejection risks. However, the intricacies and costs of producing autologous therapies present commercial challenges. The hair follicle is a multi-germ layered versatile cell source that can be harvested at any age. It is a rich source of keratinocytes, fibroblasts, multipotent stromal cells, and the newly defined Hair Follicle-Associated Pluripotent Stem Cells (HAP). It can also be obtained non-invasively and transported via regular mail channels, making it the ideal starting material for an autologous biobank. In this study, cryopreserved hair follicle-derived iPSC lines (HF-iPS) were established through integration-free vectors, encompassing a diverse cohort. These genetically stable lines exhibited robust expression of pluripotency markers, and showcased tri-lineage differentiation potential. The HF-iPSCs effectively differentiated into double-positive cKIT+/CXCR4+ definitive endoderm cells and NKX6.1+/PDX1+ pancreatic progenitor cells, affirming their pluripotent attributes. We anticipate that the use of plucked hair follicles as an accessible, non-invasive cell source to obtain patient cells, in conjunction with the use of episomal vectors for reprogramming, will improve the future generation of clinically applicable pancreatic progenitor cells for the treatment of Type I Diabetes.

Reprofiling synthetic glucocorticoid-induced leucine zipper fusion peptide as a novel and effective hair growth promoter.

Hair is a biofilament with unique multi-dimensional values. In human, in addition to physiologic impacts, hair loss and hair related disorders can affect characteristic features, emotions, and social behaviors. Despite significant advancement, there is a dire need to explore alternative novel therapies with higher efficacy, less side effects and lower cost to promote hair growth to treat hair deficiency. Glucocorticoid-induced leucine zipper (GILZ) is a protein rapidly induced by glucocorticoids. Studies from our group and many others have suggested that a synthetic form of GILZ, TAT-GILZ, a fusion peptide of trans-activator of transcription and GILZ, can function as a potent regulator of inflammatory responses, re-establishing and maintaining the homeostasis. In this study, we investigate whether TAT-GILZ could promote and contribute to hair growth. For our pre-clinical model, we used 9-12 week-old male BALB/c and nude (athymic, nu/J) mice. We applied TAT-GILZ and/or TAT (vehicle) intradermally to depilated/hairless mice. Direct observation, histological examination, and Immunofluorescence imaging were used to assess the effects and compare different treatments. In addition, we tested two current treatment for hair loss/growth, finasteride and minoxidil, for optimal evaluation of TAT-GILZ in a comparative fashion. Our results showed, for the first time, that synthetic TAT-GILZ peptide accelerated hair growth on depilated dorsal skin of BALB/c and induced hair on the skin of athymic mice where hair growth was not expected. In addition, TAT-GILZ was able to enhance hair follicle stem cells and re-established the homeostasis by increasing counter inflammatory signals including higher regulatory T cells and glucocorticoid receptors. In conclusion, our novel findings suggest that reprofiling synthetic TAT-GILZ peptide could promote hair growth by increasing hair follicle stem cells and re-establishing homeostasis.

Modeling of solar UV-induced photodamage on the hair follicles in human skin organoids.

Solar ultraviolet (sUV) exposure is known to cause skin damage. However, the pathological mechanisms of sUV on hair follicles have not been extensively explored. Here, we established a model of sUV-exposed skin and its appendages using human induced pluripotent stem cell-derived skin organoids with planar morphology containing hair follicles. Our model closely recapitulated several symptoms of photodamage, including skin barrier disruption, extracellular matrix degradation, and inflammatory response. Specifically, sUV induced structural damage and catagenic transition in hair follicles. As a potential therapeutic agent for hair follicles, we applied exosomes isolated from human umbilical cord blood-derived mesenchymal stem cells to sUV-exposed organoids. As a result, exosomes effectively alleviated inflammatory responses by inhibiting NF-κB activation, thereby suppressing structural damage and promoting hair follicle regeneration. Ultimately, our model provided a valuable platform to mimic skin diseases, particularly those involving hair follicles, and to evaluate the efficacy and underlying mechanisms of potential therapeutics.

Discovery of a novel and highly selective JAK3 inhibitor as a potent hair growth promoter.

JAK-STAT signalling pathway inhibitors have emerged as promising therapeutic agents for the treatment of hair loss. Among different JAK isoforms, JAK3 has become an ideal target for drug discovery because it only regulates a narrow spectrum of γc cytokines. Here, we report the discovery of MJ04, a novel and highly selective 3-pyrimidinylazaindole based JAK3 inhibitor, as a potential hair growth promoter with an IC50 of 2.03 nM. During in vivo efficacy assays, topical application of MJ04 on DHT-challenged AGA and athymic nude mice resulted in early onset of hair regrowth. Furthermore, MJ04 significantly promoted the growth of human hair follicles under ex-vivo conditions. MJ04 exhibited a reasonably good pharmacokinetic profile and demonstrated a favourable safety profile under in vivo and in vitro conditions. Taken together, we report MJ04 as a highly potent and selective JAK3 inhibitor that exhibits overall properties suitable for topical drug development and advancement to human clinical trials.

Melatonin promotes proliferation of Inner Mongolia cashmere goat hair follicle papilla cells through Wnt10b.

The study demonstrated that melatonin (MT) can induce the development of secondary hair follicles in Inner Mongolian cashmere goats through the Wnt10b gene, leading to secondary dehairing. However, the mechanisms underlying the expression and molecular function of Wnt10b in dermal papilla cells (DPC) remain unknown. This research aimed to investigate the impact of MT on DPC and the regulation of Wnt10b expression, function, and molecular mechanisms in DPC. The findings revealed that MT promotes DPC proliferation and enhances DPC activity. Co-culturing DPC with overexpressed Wnt10b and MT showed a significant growth promotion. Subsequent RNA sequencing (RNA-seq) of overexpressed Wnt10b and control groups unveiled the regulatory role of Wnt10b in DPC. Numerous genes and pathways, including developmental pathways such as Wnt and MAPK, as well as processes like hair follicle morphogenesis and hair cycle, were identified. These results suggest that Wnt10b promotes the growth of secondary hair follicles in Inner Mongolian cashmere goats by regulating crucial factors and pathways in DPC proliferation.

The decline in cellular iron is crucial for differentiation in keratinocytes.

Iron is a vital metal for most biological functions in tissues, and its concentration is exquisitely regulated at the cellular level. During the process of differentiation, keratinocytes in the epidermis undergo a noticeable reduction in iron content. Conversely, psoriatic lesions, characterized by disruptions in epidermal differentiation, frequently reveal an excessive accumulation of iron within keratinocytes that have undergone differentiation. In this study, we clarified the significance of attenuated cellular iron content in the intricate course of epidermal differentiation. We illustrated this phenomenon through the utilization of hinokitiol, an iron chelator derived from the heartwood of Taiwanese hinoki, which forcibly delivers iron into cells independent of the intrinsic iron-regulation systems. While primary cultured keratinocytes readily succumbed to necrotic cell death by this iron chelator, mild administration of the hinokitiol-iron complex modestly disrupts the process of differentiation in these cells. Notably, keratinocyte model cells HaCaT and anaplastic skin rudiments exhibit remarkable resilience against the cytotoxic impact of hinokitiol, and the potent artificial influx of iron explains a suppressive effect selectively on epidermal differentiation. Moreover, the augmentation of iron content induced by the overexpression of divalent metal transporter 1 culminates in the inhibition of differentiation in HaCaT cells. Consequently, the diminution in cellular iron content emerges as an important determinant influencing the trajectory of keratinocyte differentiation.

Integration Analysis of Hair Follicle Transcriptome and Proteome Reveals the Mechanisms Regulating Wool Fiber Diameter in Angora Rabbits.

Fiber diameter is an important characteristic that determines the quality and economic value of rabbit wool. This study aimed to investigate the genetic determinants of wool fiber diameter through an integration analysis using transcriptomic and proteomic datasets from hair follicles of coarse and fine wool from Angora rabbits. Using a 4D label-free technique, we identified 423 differentially expressed proteins (DEPs) in hair follicles of coarse and fine wool in Angora rabbits. Eighteen DEPs were examined using parallel reaction monitoring, which verified the reliability of our proteomic data. Functional enrichment analysis revealed that a set of biological processes and signaling pathways related to wool growth and hair diameter were strongly enriched by DEPs with fold changes greater than two, such as keratinocyte differentiation, skin development, epidermal and epithelial cell differentiation, epidermis and epithelium development, keratinization, and estrogen signaling pathway. Association analysis and protein-protein interaction network analysis further showed that the keratin (KRT) family members, including KRT77, KRT82, KRT72, KRT32, and KRT10, as well as CASP14 and CDSN, might be key factors contributing to differences in fiber diameter. Our results identified DEPs in hair follicles of coarse and fine wool and promoted understanding of the molecular mechanisms underlying wool fiber diameter variation among Angora rabbits.

Efficient Generation of Skin Organoids from Pluripotent Cells via Defined Extracellular Matrix Cues and Morphogen Gradients in a Spindle-Shaped Microfluidic Device.

Pluripotent stem cell-derived skin organoids (PSOs) emerge as a developmental skin model that is self-organized into multiple components, such as hair follicles. Despite their impressive complexity, PSOs are currently generated in the absence of 3D extracellular matrix (ECM) signals and have several major limitations, including an inverted anatomy (e.g., epidermis inside/dermis outside). In this work, a method is established to generate PSOs effectively in a chemically-defined 3D ECM environment. After examining various dermal ECM molecules, it is found that PSOs generated in collagen -type I (COLI) supplemented with laminin 511 (LAM511) exhibit increased growth compared to conventional free-floating conditions, but fail to induce complete skin differentiation due in part to necrosis. This problem is addressed by generating the PSOs in a 3D bioprinted spindle-shaped hydrogel device, which constrains organoid growth longitudinally. This culture system significantly reduces organoid necrosis and leads to a twofold increase in keratinocyte differentiation and an eightfold increase in hair follicle formation. Finally, the system is adapted as a microfluidic device to create asymmetrical gradients of differentiation factors and improves the spatial organization of dermal and epidermal cells. This study highlights the pivotal role of ECM and morphogen gradients in promoting and spatially-controlling skin differentiation in the PSO framework.

Cocktail Cell-Reprogrammed Hydrogel Microspheres Achieving Scarless Hair Follicle Regeneration.

The scar repair inevitably causes damage of skin function and loss of skin appendages such as hair follicles (HF). It is of great challenge in wound repair that how to intervene in scar formation while simultaneously remodeling HF niche and inducing in situ HF regeneration. Here, chemical reprogramming techniques are used to identify a clinically chemical cocktail (Tideglusib and Tamibarotene) that can drive fibroblasts toward dermal papilla cell (DPC) fate. Considering the advantage of biomaterials in tissue repair and their regulation in cell behavior that may contributes to cellular reprogramming, the artificial HF seeding (AHFS) hydrogel microspheres, inspired by the natural processes of "seeding and harvest", are constructed via using a combination of liposome nanoparticle drug delivery system, photoresponsive hydrogel shell, positively charged polyamide modification, microfluidic and photocrosslinking techniques. The identified chemical cocktail is as the core nucleus of AHFS. In vitro and in vivo studies show that AHFS can regulate fibroblast fate, induce fibroblast-to-DPC reprogramming by activating the PI3K/AKT pathway, finally promoting wound healing and in situ HF regeneration while inhibiting scar formation in a two-pronged translational approach. In conclusion, AHFS provides a new and effective strategy for functional repair of skin wounds.

Divergent progression pathways in male androgenetic alopecia and female pattern hair loss: Trichoscopic perspectives.

BACKGROUND: Despite similarities in progressive miniaturization of hair follicles and transition of terminal hairs to vellus hairs, insufficient trichoscopic comparisons between male androgenetic alopecia (MAGA) and female pattern hair loss (FPHL) hinder our ability to select effective treatments. AIM: Our study aimed to explore gender-specific trichoscopic characteristics of MAGA and FPHL, while formulating hypotheses regarding the progression of these conditions across clinical stages. METHODS: We classified 126 male MAGA subjects using Hamilton-Norwood Classification and 57 FPHL subjects using adopted Sinclair Scale. Subsequently, we analyzed nine trichoscopic factors divided into three categories: hair-diameter related, hair-number per follicular unit related, and hair density related factors. RESULTS: Of the nine quantitative trichoscopic factors, hair-diameter and hair-number per follicular unit showed strong correlations with clinical stages in both genders. Hair density, a common trichoscopic factor for hair loss evaluation, weakly correlated with clinical stages in FPHL, but not at all in MAGA. In addition, MAGA was characterized by a progressive reduction in hair-diameter, followed by a reduction in hair-number per follicular unit. FPHL, on the contrary, showed the opposite progression. CONCLUSIONS: Trichoscopic factors vary with disease severity in a gender-specific manner. Our research highlights that MAGA and FPHL involve two distinct streams: hair-diameter decreasing by hair follicle miniaturization (Stream 1), and hair-number per follicular unit decreasing by hair follicle tri-lineage niche dysfunction (Stream 2). MAGA typically starts from Stream 1 to Stream 2, while FPHL starts from Stream 2. These diverse progression pathways underscore the importance of personalized treatment approaches.

Exosomes for hair growth and regeneration.

Exosomes are lipid bilayer vesicles, 30-200 nm in diameter, that are produced by cells and play essential roles in cell-cell communication. Exosomes have been studied in several medical fields including dermatology. Hair loss, a major disorder that affects people and sometimes causes mental stress, urgently requires more effective treatment. Because the growth and cycling of hair follicles are governed by interactions between hair follicle stem cells (HFSCs) and dermal papilla cells (DPCs), a better understanding of the mechanisms responsible for hair growth and cycling through exosomes may provide new insights into novel treatments for hair loss. In this review, we focused on the comprehensive knowledge and recent studies on exosomes in the field of hair development and regeneration. We classified exosomes of several cellular origins for the treatment of hair loss. Exosomes and their components, such as microRNAs, are promising drugs for effective hair loss treatment.

Generation and characterization of a Dkk4-Cre knock-in mouse line.

Ectodermal appendages in mammals, such as teeth, mammary glands, sweat glands and hair follicles, are generated during embryogenesis through a series of mesenchymal-epithelial interactions. Canonical Wnt signaling and its inhibitors are implicated in the early steps of ectodermal appendage development and patterning. To study the activation dynamics of the Wnt target and inhibitor Dickkopf4 (Dkk4) in ectodermal appendages, we used CRSIPR/Cas9 to generate a Dkk4-Cre knock-in mouse (Mus musculus) line, where the Cre recombinase cDNA replaces the expression of endogenous Dkk4. Using Cre reporters, the Dkk4-Cre activity was evident at the prospective sites of ectodermal appendages, overlapping with the Dkk4 mRNA expression. Unexpectedly, a predominantly mesenchymal cell population in the embryo posterior also showed Dkk4-Cre activity. Lineage-tracing suggested that these cells are likely derived from a few Dkk4-Cre-expressing cells in the epiblast at early gastrulation. Finally, our analyses of Dkk4-Cre-expressing cells in developing hair follicle epithelial placodes revealed intra- and inter-placodal cellular heterogeneity, supporting emerging data on the positional and transcriptional cellular variability in placodes. Collectively, we propose the new Dkk4-Cre knock-in mouse line as a suitable model to study Wnt and DKK4 inhibitor dynamics in early mouse development and ectodermal appendage morphogenesis.

Evaluation of noninvasive biospecimens for transcriptome studies.

Transcriptome studies disentangle functional mechanisms of gene expression regulation and may elucidate the underlying biology of disease processes. However, the types of tissues currently collected typically assay a single post-mortem timepoint or are limited to investigating cell types found in blood. Noninvasive tissues may improve disease-relevant discovery by enabling more complex longitudinal study designs, by capturing different and potentially more applicable cell types, and by increasing sample sizes due to reduced collection costs and possible higher enrollment from vulnerable populations. Here, we develop methods for sampling noninvasive biospecimens, investigate their performance across commercial and in-house library preparations, characterize their biology, and assess the feasibility of using noninvasive tissues in a multitude of transcriptomic applications. We collected buccal swabs, hair follicles, saliva, and urine cell pellets from 19 individuals over three to four timepoints, for a total of 300 unique biological samples, which we then prepared with replicates across three library preparations, for a final tally of 472 transcriptomes. Of the four tissues we studied, we found hair follicles and urine cell pellets to be most promising due to the consistency of sample quality, the cell types and expression profiles we observed, and their performance in disease-relevant applications. This is the first study to thoroughly delineate biological and technical features of noninvasive samples and demonstrate their use in a wide array of transcriptomic and clinical analyses. We anticipate future use of these biospecimens will facilitate discovery and development of clinical applications.

A histological study of the facial hair follicles in the pygmy sperm whale (Kogia breviceps).

In the pygmy sperm whale (Kogia breviceps, Blainville 1838), vibrissae are present in neonates, but within a few months the hairs are lost, and the structures remain as empty vibrissal crypts (VCs). In this work, we have studied histologically the facial vibrissal follicles of two juveniles and one adult specimens stranded dead. A few VCs with no visible hairs were found grouped in a row rostral to each eye. The follicular lumen, covered by a simple squamous epithelium, showed invaginations in the most superficial part. Beneath the epithelium, the follicle walls were made of loose connective tissue and were encircled by a thick capsule of dense connective tissue. In juveniles, a dermal papilla was found basally and, from it, a non-keratinized pseudo hair grew upwards but did not reach the skin surface. The VCs were richly innervated and irrigated. Many lamellated corpuscles were identified in the subluminal connective tissue of the crypt walls. A large venous cavernous plexus was located beneath and around the hair papilla. The main differences observed in the adult specimen were the degeneration and calcification of both the dermal papilla and the pseudo hair, and the absence of the venous cavernous plexus, albeit maintaining a rich vascularization and innervation. Our study revealed that VCs of the pygmy sperm whale possess features of fully functional sensory structures, with a microanatomy different from those described in other species. In addition, they undergo a postnatal morphological transformation, which implies functional differences between the VCs of neonates and adults.

Multi-Stage Transcriptome Analysis Revealed the Growth Mechanism of Feathers and Hair Follicles during Induction Molting by Fasting in the Late Stage of Egg Laying.

Induced molting is a common method to obtain a new life in laying hens, in which periodic changes in feathers are the prominent feature. Nevertheless, its precise molecular mechanism remains unclear. In this study, feather and hair follicle samples were collected during fasting-induced physiological remodeling for hematoxylin-eosin staining, hormone changes and follicle traits, and transcriptome sequencing. Feather shedding was observed in F13 to R25, while newborns were observed in R3 to R32. Triiodothyronine and tetraiodothyronine were significantly elevated during feather shedding. The calcium content was significantly higher, and the ash content was significantly lower after the changeover. The determination of hair follicle traits revealed an increasing trend in pore density and a decrease in pore diameter after the resumption of feeding. According to RNA-seq results, several core genes were identified, including DSP, CDH1, PKP1, and PPCKB, which may have an impact on hair follicle growth. The focus was to discover that starvation may trigger changes in thyroid hormones, which in turn regulate feather molting through thyroid hormone synthesis, calcium signaling, and thyroid hormone signaling pathways. These data provide a valuable resource for the analysis of the molecular mechanisms underlying the cyclical growth of hair follicles in the skin during induced molting.

Regulation of secondary hair follicle cycle in cashmere goats by miR-877-3p targeting IGFBP5 gene.

Cashmere, a highly valuable animal product derived from cashmere goats, holds significant economic importance. MiRNAs serve as crucial regulators in the developmental processes of mammalian hair follicles. Understanding the regulation of miRNAs during the hair follicle cycle is essential for enhancing cashmere quality. In this investigation, we employed high-throughput sequencing technology to analyze the expression profiles of miRNAs in the secondary hair follicles of Jiangnan cashmere goats at different stages. Through bioinformatics analysis, we identified differentially expressed miRNAs (DE miRNAs). The regulatory relationships between miRNAs and their target genes were verified using multiple techniques, including RT-qPCR, western blot, Dual-Luciferase Reporter, and CKK-8 assays. Our findings revealed the presence of 193 DE miRNAs during various stages of the hair follicle cycle in Jiangnan cashmere goats. Based on the previously obtained mRNA data, the target genes of DE miRNA were predicted, and 1,472 negative regulatory relationships between DE miRNAs and target genes were obtained. Notably, the expression of chi-miR-877-3p was down-regulated during the telogen (Tn) phase compared to the anagen (An) and catagen (Cn) phases, while the IGFBP5 gene exhibited up-regulation. Further validation experiments confirmed that overexpression of chi-miR-877-3p in dermal papilla cells suppressed IGFBP5 gene expression and facilitated cell proliferation. The results of this study provide novel insights for analyzing the hair follicle cycle.

Cashmere goats, known for their diverse range of animal products including delectable meat, soft sheepskin, and high-quality natural fiber, offer an excellent opportunity to explore hair regeneration as they represent a heterogenous fur mammal. MicroRNAs (miRNAs) are small non-coding RNA molecules encoded by approximately 3% of mammalian genes. Remarkably, they have the ability to regulate around 30% of protein-coding genes. Given that a single miRNA can target multiple genes, they exert control over various biological functions such as metabolism, growth, development, and immunity. In this study, we found that miR-877-3p is able to regulate the expression of insulin-like growth factor binding protein 5 (IGFBP5), a key gene involved in the development of the hair follicle cycle. Investigating the regulatory role of miRNAs in the hair follicle cycle of cashmere goats provides a novel perspective for unraveling the mechanisms underlying hair follicle growth and development in mammals.