The role of cell-cell and cell-matrix junctional complexes in sebaceous gland homeostasis and differentiation.

Sebaceous glands (SG) are essential for maintaining skin integrity, as their lipid-rich secretion (sebum) lubricates and protects the epidermis and hairs. In addition, these glands have an emerging role in immunomodulation and may affect whole-body energy metabolism, besides being an appealing model for research in topics as lipogenesis, stem cell biology and tumorigenesis. In spite of the increasing interest in studying SGs pathophysiology, sebocyte cell-cell and cell-matrix adhesion processes have been only superficially examined, and never in a systematic way. This is regrettable considering the key role of cellular adhesion in general, the specific expression pattern of indivdual junctional complexes, and the reports of structural changes in SGs after altered expression of adhesion-relevant proteins. Here, we review the available information on structural and functional aspects of cell-cell and cell-matrix junctions in sebocytes, and how these processes change under pathological conditions. This information will contribute for better understanding sebocyte differentiation and sebum secretion, and may provide hints for novel therapeutic strategies for skin diseases.

5-Aminolaevulinic acid-based photodynamic therapy suppresses lipid secretion by inducing mitochondrial stress and oxidative damage in sebocytes and ameliorates ear acne in mice.

Acne is a chronic inflammatory skin disease with wide-ranging effects, involving factors such as Propionibacterium acnes (P. acnes) infection and sebum hypersecretion. Current acne treatments are challenged by drug resistance. 5-aminolaevulinic acid (ALA) -based photodynamic therapy (PDT) has been widely used in the clinical treatment of acne, however, the mechanism of its action remains to be elucidated. In this study, by constructing a mice ears model of P. acnes infection, we found that ALA-PDT inhibited the proliferation of P. acnes in vivo and in vitro, significantly ameliorated ear swelling, and blocked the chronic inflammatory process. In vitro, ALA-PDT inhibited lipid secretion and regulated the expression of lipid synthesis and metabolism-related genes in SZ95 cells. Further, we found that ALA-PDT led to DNA damage and apoptosis in SZ95 cells by inducing mitochondrial stress and oxidative stress. Altogether, our study demonstrated the great advantages of ALA-PDT for the treatment of acne and revealed that the mechanism may be related to the blockade of chronic inflammation and the suppression of lipid secretion by ALA-PDT.

Ozenoxacin suppresses sebum production by inhibiting mTORC1 activation in differentiated hamster sebocytes.

Acne vulgaris is a complex condition involving factors that affect the pilosebaceous unit. A primary manifestation of acne pathology is the development of comedones, often linked to the overproduction of sebum resulting from 5α-dihydrotestosterone (5α-DHT) and insulin activity. Ozenoxacin is a topical quinolone that exhibits potent antibacterial activity against Cutibacterium acnes (C. acnes). It is commonly used to treat acne associated with this bacterium; however, its effect on sebum production within the sebaceous glands remains unclear. In this study, the effects of ozenoxacin on sebum production were examined using insulin- and 5α-DHT-differentiated hamster sebocytes. Ozenoxacin showed a dose-dependent inhibition of lipid droplet formation and triacylglycerol (TG) production, which is a major component of sebum. In addition, it suppressed the expression of diacylglycerol acyltransferase 1, stearoyl-CoA desaturase-1, and perilipin-1 mRNA, all important factors involved in sebum synthesis, in a dose-dependent manner. Moreover, ozenoxacin decreased phosphorylated 40S ribosomal protein S6 levels downstream of the mechanistic/mammalian target of rapamycin complex 1 (mTORC1), without altering the phosphorylation of Akt, an upstream regulator of mTORC1, in both insulin- and 5α-DHT-treated hamster sebocytes. Interestingly, nadifloxacin, but not clindamycin, exhibited a similar suppression of sebum production, albeit with lesser potency compared with ozenoxacin. Furthermore, a topical application of a 2% ozenoxacin-containing lotion to the auricle skin of hamsters did not affect the size of the sebaceous glands or epidermal thickness. Notably, it decreased the amount of TG on the skin surface. The results provide novel insights into the sebum-inhibitory properties of ozenoxacin, indicating its potential efficacy in controlling microbial growth and regulating sebum production for acne management.

Microchanneling and ultrasonic delivery of gold and platinum nanoparticles for selective photothermolysis of sebaceous follicles in the treatment of acne: a pilot study using porcine skin.

PURPOSE: Several treatment options for acne vulgaris are limited by their associated adverse effects. An innovative approach involves introducing light-absorbing nanoparticles into sebaceous follicles before destroying the follicles using selective photothermolysis. We aimed to investigate efficient methods for introducing gold and platinum nanoparticles into sebaceous follicles and to identify suitable laser equipment and parameters for the effective destruction of these follicles. METHODS: We used porcine skin as the experimental model. We compared the efficacies of a thulium laser, ultrasound, and manual massage and evaluated the optimal method for delivering nanoparticles in close proximity to sebaceous follicles. Subsequently, a 1064-nm-wavelength neodymium-doped yttrium aluminum garnet (Nd: YAG) laser was employed to induce selective photothermolysis. We compared different parameters to identify the optimal pulse duration and fluence of the Nd: YAG laser. The extent of penetration and destruction of sebaceous follicles was assessed using hematoxylin and eosin (H&E) staining, and a numerical evaluation was conducted. RESULTS: H&E staining showed that irradiation with a long-pulsed Nd: YAG laser following a combination of thulium laser and sonophoresis effectively destroyed sebaceous follicles, with destruction rates exceeding 50%. These results were valid with a long pulse duration and a high fluence of the Nd: YAG laser. CONCLUSION: This study demonstrated that sebaceous follicles can be effectively destroyed through a mixture of gold and platinum nanoparticle delivery by a combination of microchanneling and sonophoresis, followed by selective thermal damage induced by a 1064-nm long-pulsed high-fluence Nd: YAG laser.

Morphological and biochemical characterization of Holstein cow skin at the tail root region susceptible to Chorioptes bovis and texanus parasitism.

Cattle mange causes extreme itchiness, and the associated stress is an animal welfare concern that leads to economic losses due to decreased cattle productivity and deworming costs. This study investigated the reason why Chorioptic mites, C. bovis and C. texanus, preferentially infest the tail root region (rTR) and performed histological and biochemical analysis focusing on the volatile components of host odors that serve as the starting point for infestation of parasitic arthropods. Skin samples were taken from the rTR, lateral abdominal, and central masseteric, with the latter two designated as comparison sites. The two and three-dimensional histological analysis measured each sebaceous and sweat gland percentage per unit volume. The q-PCR analyzed the expression levels of ALDH1A1 and LOC785756, which are genes associated with volatile odoriferous compounds that serve as repellency and attractive messengers for ticks. Immunohistochemistry stained three sites with anti-androgen binding protein beta-like (ABPß-like), encoded by LOC785756, antibody. The three-dimensional analysis showed that sebaceous glands in the rTR tend to be more continuous and existed in larger masses than in other regions. The expression level of LOC785756 was significantly higher in the rTR, and immunohistochemistry revealed the presence of ABPß-like in the sebaceous gland with strong positive signals in the rTR. These results suggest that C. bovis/texanus selectively infests the rTR because that skin has well-developed sebaceous glands, including a large amount of ABPß-like, which acts as a mite attractant.

Targeting sebaceous glands: a review of selective photothermolysis for Acne Vulgaris treatment.

Acne vulgaris (AV), characterized by excessive sebum production and Cutibacterium acnes proliferation in the sebaceous glands, significantly impacts physical and psychological health. Recent treatment advancements have focused on selective photothermolysis of sebaceous glands. This review evaluates two innovative therapies: the 1726-nm laser and nanoparticle-assisted laser treatments. We conducted a comprehensive search of PubMed and Embase using the primary terms "acne vulgaris" or "acne" AND "laser," "photothermal therapy," "nanoparticles," "treatment," or "1726 nm laser." Inclusion criteria were articles published in English in peer-reviewed journals that focused on treating AV through targeting the sebaceous glands, yielding 11 studies. Gold nanoparticles, used with 800-nm laser, 1064-nm Nd: YAG laser, or photopneumatic device, and platinum nanoparticles with 1450-nm diode laser, showed notable improvements in severity and number of acne lesions, safety, and patient satisfaction. The 1726-nm laser treatments also showed considerable lesion reduction and tolerability, with minimal side effects such as erythema and edema. Its efficiency is credited to its short, high-power pulses that effectively target sebaceous glands, offering precise treatment with fewer side effects compared to lower-power pulses. Selective photothermolysis using nanoparticle-assisted laser therapy or the 1726-nm laser offers a promising alternative to conventional AV treatments, showcasing efficacy and high patient satisfaction. The 1726-nm laser streamlines treatment but involves new equipment costs, while nanoparticle-assisted therapy integrates well into existing setups but relies on external agents and is unsuitable for certain allergies. Future research should include long-term studies and comparative analyses. The choice of treatment modality should consider patient preferences, cost implications, and availability of specific therapies.

A spatial portrait of the human sebaceous gland transcriptional program.

Sebaceous glands (SG) and their oily secretion (sebum) are indispensable for maintaining skin structure and function, and their deregulation causes skin disorders including but not limited to acne. Recent studies also indicate that sebum may have important immunomodulatory activities and may influence whole-body energy metabolism. However, the progressive transcriptional changes of sebocytes that lead to sebum production have never been characterized in detail. Here, we exploited the high cellular resolution provided by sebaceous hyperplasia and integrated spatial transcriptomics, pseudo time analysis, RNA velocity, and functional enrichment to map the landscape of sebaceous differentiation. Our results were validated by comparison with published SG transcriptome data and further corroborated by assessing the protein expression pattern of a subset of the transcripts in the public repository Human Protein Atlas. Departing from four sebocyte differentiation stages generated by unsupervised clustering, we demonstrate consecutive modulation of cellular functions associable with specific gene sets, from cell proliferation and oxidative phosphorylation via lipid synthesis to cell death. Both validation methods confirmed the biological significance of our results. Our report is complemented by a freely available and browsable online tool. Our data provide the first high-resolution spatial portrait of the SG transcriptional landscape and deliver starting points for experimentally assessing novel candidate molecules for regulating SG homeostasis in health and disease.

A novel H­tert immortalized human sebaceous gland cell line (XL-i-20) for the investigation of photodynamic therapy.

BACKGROUND: Acne vulgaris is a species-specific human disease. To date, there has been no established human sebocyte cell line of Asian origin. Our previous study has demonstrated the efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in the treatment of acne vulgaris, primarily attributed to its cytotoxic properties; however, its regulatory mechanism remains largely unknown. OBJECTIVES: To establish an immortalized human sebocyte cell line derived from Chinese population and investigate the underlying mechanism of ALA-PDT. METHODS: Human primary sebocytes were transfected with the human tert gene (h­tert). The biological characteristics, including cell proliferation, cell markers, and sebum secretion function, were compared between primary sebocytes and the immortalized sebocytes (XL-i-20). Stimulations such as ALA-PDT, were applied respectively to both primary sebocytes and XL-i-20 cells to assess changes in their cellular functions. The transcriptome differences between primary sebocytes and XL-i-20 sebocytes were investigated using RNA-seq analysis. The XL-i-20 cell line was used to establish a sebaceous gland (SG) organoid culture, serving as a representative model of SG for the investigation of ALA-PDT. RESULTS: The h­tert immortalized sebocyte cell line exhibited the ability to be consecutively cultured for more than fifty passages. Both primary and immortalized cells expressed sebocyte markers such as epithelial membrane antigens (EMA, or MUC-1), Cytokeratin 7 (CK7) and adipose differentiation-related protein associated antigens (ADRP), and maintained sebum secretion function. The proliferative capacity of XL-i-20 was found to be significantly higher than that of primary sebocytes. The responses of XL-i-20 to ALA-PDT were indistinguishable from those elicited by primary sebocytes. Cell viability and sebum secretion were decreased after ALA-PDT in both two cell lines, and lipid-related proteins (SREBP-1/PPARγ) were down-regulated. The transcriptome data consistently demonstrated upregulation of genes related to inflammatory responses and downregulation of genes involved in lipid metabolism in both cell types following PDT. The analysis of common differential genes of primary sebocytes and XL-i-20 sebocytes post ALA-PDT showed that TNF signaling pathways, MAPK signaling pathways and JAK-STAT signaling pathways were activated. The SG organoids were spherical, which expressed markers of FANS and PLET1. Ki-67 was down-regulated after ALA-PDT. CONCLUSIONS: We have developed an h­tert immortalized sebocyte cell line from an Asian population. The cell line, XL-i-20, maintains the essential characteristics of its parent primary sebocytes. Moreover, XL-i-20 sebocyte exhibited a significant respond to ALA-PDT, demonstrating comparable phenotypic and molecular changes to primary sebocytes. Therefore, XL-i-20 and its derived SG organoid serve as appropriate in vitro models for investigating the efficacy and mechanisms of ALA-PDT in SG-related diseases.

Potential of cannabidiol as acne and acne scar treatment: novel insights into molecular pathways of pathophysiological factors.

Cannabidiol (CBD), which is derived from hemp, is gaining recognition because of its anti-inflammatory and lipid-modulating properties that could be utilized to treat acne. We conducted experiments to quantitatively assess the effects of CBD on acne-related cellular pathways. SEB-1 sebocytes and HaCaT keratinocytes were exposed to various CBD concentrations. CBD exhibited a concentration-dependent impact on cell viability and notably reduced SEB-1 viability; furthermore, it induced apoptosis and a significant increase in the apoptotic area at higher concentrations. Additionally, CBD remarkably reduced pro-inflammatory cytokines, including CXCL8, IL-1α, and IL-1ß. Additionally, it inhibited lipid synthesis by modulating the AMPK-SREBP-1 pathway and effectively reduced hyperkeratinization-related protein keratin 16. Simultaneously, CBD stimulated the synthesis of elastin, collagen 1, and collagen 3. These findings emphasize the potential of CBD for the management of acne because of its anti-inflammatory, apoptotic, and lipid-inhibitory effects. Notably, the modulation of the Akt/AMPK-SREBP-1 pathway revealed a novel and promising mechanism that could address the pathogenesis of acne.

Benign mixed mammary tumor with sebaceous differentiation in a dog.

We describe here a case of canine mammary benign mixed tumor with sebaceous metaplasia in the right fifth mammary gland of an eight-year-old, intact female Poodle dog. Grossly, the mass was firm with off-white, poorly lobulated cut surfaces. Histologically, the luminal epithelial cells and myoepithelial cells proliferated with cartilage formation and focal squamous metaplasia. Moreover, a large number of nests of various sizes, which were filled with foamy cells in the center and associated with basaloid reserve-like cells in the periphery, showed sebaceous gland-like structures. Immunohistochemically, myoepithelial cells and reserve-like cells in the metaplastic sebaceous gland-like structures were CK14, α-smooth muscle actin (α-SMA) and p63 positive, suggesting a possibility that these two components may have a common cell of origin.

TRPV3 promotes sebocyte inflammation via transcriptional modulating TLR2 in acne.

Acne is a common chronic inflammatory disease of the pilosebaceous unit. Transient receptor potential vanilloid 3 (TRPV3) is an ion channel that is involved in inflammatory dermatosis development. However, the involvement of TRPV3 in acne-related inflammation remains unclear. Here, we used acne-like mice and human sebocytes to examine the role of TRPV3 in the development of acne. We found that TRPV3 expression increased in the skin lesions of Propionibacterium acnes (P. acnes)-injected acne-like mice and the facial sebaceous glands (SGs) of acne patients. TRPV3 promoted inflammatory cytokines and chemokines secretion in human sebocytes and led to neutrophil infiltration surrounding the SGs in acne lesions, further exacerbating sebaceous inflammation and participating in acne development. Mechanistically, TRPV3 enhanced TLR2 level by promoting transcriptional factor phosphorylated-FOS-like antigen-1 (p-FOSL1) expression and its binding to the TLR2 promoter, leading to TLR2 upregulation and downstream NF-κB signaling activation. Genetic or pharmacological inhibition of TRPV3 both alleviated acne-like skin inflammation in mice via the TLR2-NF-κB axis. Thus, our study revealed the critical role of TRPV3 in sebaceous inflammation and indicated its potential as an acne therapeutic target.

Sebaceous gland atrophy due to seborrheic dermatitis in a patient with alopecia: A potential pitfall.

Seborrheic dermatitis is an inflammatory condition that usually presents with erythema, scaly greasy papules, and plaques affecting sebaceous gland-rich areas and predominantly involving the face and scalp. The diagnosis of seborrheic dermatitis can often be rendered based on the clinical presentation. However, in certain cases, a biopsy can be useful to distinguish it from clinical mimics such as psoriasis, discoid lupus, and rosacea. Prominent sebaceous gland atrophy without scarring has been well-described as an important and relatively specific clue for psoriatic or drug-induced alopecia. However, sebaceous gland atrophy is not specific to psoriasis and has been demonstrated in seborrheic dermatitis, facial discoid dermatitis, and potentially may occur in other inflammatory dermatoses of the scalp. We report a 23-year-old female patient presenting with non-scarring hair loss and histopathological findings demonstrating mild androgenetic alopecia and changes of seborrheic dermatitis with dramatic sebaceous gland atrophy. The patient had no history or evidence of psoriasis clinically. Our case suggests that in patients with seborrheic dermatitis, sebaceous gland atrophy may complicate the evaluation of alopecia biopsies and should be recognized as a pitfall. Seborrheic dermatitis should be included in the differential diagnosis of alopecia biopsies showing prominent sebaceous gland atrophy.

Spatial transcriptomics reveals altered lipid metabolism and inflammation-related gene expression of sebaceous glands in psoriasis and atopic dermatitis.

Sebaceous glands drive acne, however, their role in other inflammatory skin diseases remains unclear. To shed light on their potential contribution to disease development, we investigated the spatial transcriptome of sebaceous glands in psoriasis and atopic dermatitis patients across lesional and non-lesional human skin samples. Both atopic dermatitis and psoriasis sebaceous glands expressed genes encoding key proteins for lipid metabolism and transport such as ALOX15B, APOC1, FABP7, FADS1/2, FASN, PPARG, and RARRES1. Also, inflammation-related SAA1 was identified as a common spatially variable gene. In atopic dermatitis, genes mainly related to lipid metabolism (e.g. ACAD8, FADS6, or EBP) as well as disease-specific genes, i.e., Th2 inflammation-related lipid-regulating HSD3B1 were differentially expressed. On the contrary, in psoriasis, more inflammation-related spatially variable genes (e.g. SERPINF1, FKBP5, IFIT1/3, DDX58) were identified. Other psoriasis-specific enriched pathways included lipid metabolism (e.g. ACOT4, S1PR3), keratinization (e.g. LCE5A, KRT5/7/16), neutrophil degranulation, and antimicrobial peptides (e.g. LTF, DEFB4A, S100A7-9). In conclusion, our results show that sebaceous glands contribute to skin homeostasis with a cell type-specific lipid metabolism, which is influenced by the inflammatory microenvironment. These findings further support that sebaceous glands are not bystanders in inflammatory skin diseases, but can actively and differentially modulate inflammation in a disease-specific manner.

Comparative Characterization of Human Meibomian Glands, Free Sebaceous Glands, and Hair-Associated Sebaceous Glands Based on Biomarkers, Analysis of Secretion Composition, and Gland Morphology.

Meibomian gland dysfunction (MGD) is one of the main causes of dry eye disease. To better understand the physiological functions of human meibomian glands (MGs), the present study compared MGs with free sebaceous glands (SGs) and hair-associated SGs of humans using morphological, immunohistochemical, and liquid chromatography-mass spectrometry (LCMS)-based lipidomic approaches. Eyelids with MGs, nostrils, lips, and external auditory canals with free SGs, and scalp with hair-associated SGs of body donors were probed with antibodies against cytokeratins (CK) 1, 8, 10, and 14, stem cell markers keratin 15 and N-cadherin, cell-cell contact markers desmoglein 1 (Dsg1), desmocollin 3 (Dsc3), desmoplakin (Dp), plakoglobin (Pg), and E-cadherin, and the tight junction protein claudin 5. In addition, Oil Red O staining (ORO) was performed in cryosections. Secretions of MGs as well as of SGs of nostrils, external auditory canals, and scalps were collected from healthy volunteers, analyzed by LCMS, and the data were processed using various multivariate statistical analysis approaches. Serial sections of MGs, free SGs, and hair-associated SGs were 3D reconstructed and compared. CK1 was expressed differently in hair-associated SGs than in MGs and other free SGs. The expression levels of CK8, CK10, and CK14 in MGs were different from those in hair-associated SGs and other free SGs. KRT15 was expressed differently in hair-associated SGs, whereas N-cadherin was expressed equally in all types of glands. The cell-cell contact markers Dsg1, Dp, Dsc3, Pg, and E-cadherin revealed no differences. ORO staining showed that lipids in MGs were more highly dispersed and had larger lipid droplets than lipids in other free SGs. Hair-associated SGs had a smaller number of lipid droplets. LCMS revealed that the lipid composition of meibum was distinctively different from that of the sebum of the nostrils, external auditory canals, and scalp. The 3D reconstructions of the different glands revealed different morphologies of the SGs compared with MGs which are by far the largest type of glands. In humans, MGs differ in their morphology and secretory composition and show major differences from free and hair-associated SGs. The composition of meibum differs significantly from that of sebum from free SGs and from hair-associated SGs. Therefore, the MG can be considered as a highly specialized type of holocrine gland that exhibits all the histological characteristics of SGs, but is significantly different from them in terms of morphology and lipid composition.

Biosignatures of defective sebaceous gland activity in sebum-rich and sebum-poor skin areas in adult atopic dermatitis.

Atopic dermatitis (AD) is a composite disease presenting disruption of the skin permeability barrier (SPB) in the stratum corneum (SC). Recent evidence supports derangement of the sebaceous gland (SG) activity in the AD pathomechanisms. The objective of this study was to delineate profiles of both sebaceous and epidermal lipids and of aminoacids from SG-rich (SGR) and SG-poor (SGP) areas in AD. Both sebum and SC were sampled from SGR areas, while SC was sampled also from SGP areas in 54 adult patients with AD, consisting of 34 and 20 subjects, respectively with and without clinical involvement of face, and in 44 age and sex-matched controls. Skin biophysics were assessed in all sampling sites. Disruption of the SBP was found to be associated with dysregulated lipidome. Abundance of sapienate and lignocerate, representing, respectively, sebum and the SC type lipids, were decreased in sebum and SC from both SGR and SGP areas. Analogously, squalene was significantly diminished in AD, regardless the site. Extent of lipid derangement in SGR areas was correlated with the AD severity. The abundance of aminoacids in the SC from SGR areas was altered more than that determined in SGP areas. Several gender-related differences were found in both controls and AD subgroups. In conclusion, the SG activity was differently compromised in adult females and males with AD, in both SGR and SGP areas. In AD, alterations in the aminoacidome profiles were apparent in the SGR areas. Lipid signatures in association with aminoacidome and skin physical properties may serve the definition of phenotype clusters that associate with AD severity and gender.

ALA-PDT promotes IL-1ß secretion from human SZ95 sebocytes via activation of the NLRP3 inflammasome.

BACKGROUND: 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) is an effective treatment for pilosebaceous inflammatory diseases, such as acne vulgaris. In this study, we explored ALA-PDT's mechanisms against acne in vitro. METHODS: We treated human SZ95 sebocytes with ALA (0.2 mM) and subjected them to varied PDT doses (0, 5, 10, 20 J/cm²) over 12 h. We assessed cell viability post-treatment using the Annexin V FITC/PI apoptosis kit. ROS accumulation in the sebocytes was detected with a DCFDA probe. We quantified NLRP3 and caspase-1 mRNA via quantitative PCR and determined IL-1ß release following ALA-PDT by ELISA. Western blotting helped identify the levels of proteins associated with pyroptosis (NLRP3, caspase-1, and IL-1ß). To elucidate the mechanisms, we re-evaluated these parameters after administering various concentrations of NAC antioxidants (0, 0.4, 2, 10 mM) and the caspase inhibitor Z-VAD-FMK (0, 5, 10, 20 µM). RESULTS: Increasing PDT dose inversely affected SZ95 sebocyte survival, with a corresponding rise in ROS and pyroptosis-related proteins (NLRP3, caspase-1, and IL-1ß). Furthermore, NAC and Z-VAD-FMK modulated the expression and secretion of these molecules in a dose-responsive manner. CONCLUSION: Our findings suggest ALA-PDT's potential mechanism of action on sebaceous glands could involve ROS induction, leading to NLRP3 inflammasome assembly, thereby heightening caspase-1 activation and IL-1ß secretion. This cascade may amplify the local inflammatory response to break chronic inflammation in acne vulgaris treatment.

Skin single-cell transcriptomics reveals a core of sebaceous gland-relevant genes shared by mice and humans.

BACKGROUND: Single-cell RNA sequencing (scRNA-seq) has been widely applied to dissect cellular heterogeneity in normal and diseased skin. Sebaceous glands, essential skin components with established functions in maintaining skin integrity and emerging roles in systemic energy metabolism, have been largely neglected in scRNA-seq studies. METHODS: Departing from mouse and human skin scRNA-seq datasets, we identified gene sets expressed especially in sebaceous glands with the open-source R-package oposSOM. RESULTS: The identified gene sets included sebaceous gland-typical genes as Scd3, Mgst1, Cidea, Awat2 and KRT7. Surprisingly, however, there was not a single overlap among the 100 highest, exclusively in sebaceous glands expressed transcripts in mouse and human samples. Notably, both species share a common core of only 25 transcripts, including mitochondrial and peroxisomal genes involved in fatty acid, amino acid, and glucose processing, thus highlighting the intense metabolic rate of this gland. CONCLUSIONS: This study highlights intrinsic differences in sebaceous lipid synthesis between mice and humans, and indicates an important role for peroxisomal processes in this context. Our data also provides attractive starting points for experimentally addressing novel candidates regulating sebaceous gland homeostasis.

High incidence of sebaceous gland inflammation in aldose reductase-deficient mice.

Aldose reductase is a member of the 1B1 subfamily of aldo-keto reductase gene superfamily. The action of aldose reductase (AR) has been implicated in the pathogenesis of a variety of disease states, most notably complications of diabetes mellitus including neuropathy, retinopathy, nephropathy, and cataracts. To explore for mechanistic roles for AR in disease pathogenesis, we established mutant strains produced using Crispr-Cas9 to inactivate the AKR1B3 gene in C57BL6 mice. Phenotyping AR-knock out (ARKO) strains confirmed previous reports of reduced accumulation of tissue sorbitol levels. Lens epithelial cells in ARKO mice showed markedly reduced epithelial-to-mesenchymal transition following lens extraction in a surgical model of cataract and posterior capsule opacification. A previously unreported phenotype of preputial sebaceous gland swelling was observed frequently in male ARKO mice homozygous for the mutant AKR1B3 allele. This condition, which was shown to be accompanied by infiltration of proinflammatory CD3+ lymphocytes, was not observed in WT mice or mice heterozygous for the mutant allele. Despite this condition, reproductive fitness of the ARKO strain was indistinguishable from WT mice housed under identical conditions. These studies establish the utility of a new strain of AKR1B3-null mice created to support mechanistic studies of cataract and diabetic eye disease.

Alcohol Promotes Lipogenesis in Sebocytes-Implications for Acne.

The oral consumption of alcohol (ethanol) has a long tradition in humans and is an integral part of many cultures. The causal relationship between ethanol consumption and numerous diseases is well known. In addition to the well-described harmful effects on the liver and pancreas, there is also evidence that ethanol abuse triggers pathological skin conditions, including acne. In the present study, we addressed this issue by investigating the effect of ethanol on the energy metabolism in human SZ95 sebocytes, with particular focus on qualitative and quantitative lipogenesis. It was found that ethanol is a strong trigger for lipogenesis, with moderate effects on cell proliferation and toxicity. We identified the non-oxidative metabolism of ethanol, which produced fatty acid ethyl esters (FAEEs), as relevant for the lipogenic effect-the oxidative metabolism of ethanol does not contribute to lipogenesis. Correspondingly, using the Seahorse extracellular flux analyzer, we found an inhibition of the mitochondrial oxygen consumption rate as a measure of mitochondrial ATP production by ethanol. The ATP production rate from glycolysis was not affected. These data corroborate that ethanol-induced lipogenesis is independent from oxygen. In sum, our results give a causal explanation for the prevalence of acne in heavy drinkers, confirming that alcoholism should be considered as a systemic disease. Moreover, the identification of key factors driving ethanol-dependent lipogenesis may also be relevant in the treatment of acne vulgaris.

Sebaceous carcinoma with apocrine differentiation arising in a known case of basal cell carcinoma: A rare entity.

Sebaceous carcinoma is a ra malignant tumor of adnexal origin arising from sebaceous glands. It is most commonly seen arising from the eyelids and head and neck. It is predominantly seen in females with an average age of around 65 years. Apocrine differentiation in sebaceous carcinomas is rare but has been reported in the literature. Here, we present a case of sebaceous carcinoma with apocrine differentiation in a 62-year- old female who was a diagnosed case of basal cell carinoma.