Androgens induce sebaceous differentiation in sebocyte cells expressing a stable functional androgen receptor

Barrault, C.; Garnier, Julien; Pedretti, Nathalie; Cordier-Dirikoc, Sevda; Ratineau, Emeline; Deguercy, Alain; Bernard, François‐Xavier

doi:10.1016/j.jsbmb.2015.04.005

Cited by 43 publications

(37 citation statements)

References 30 publications

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“…Desaturase enzymes regulate unsaturation of fatty acids by introducing double bonds between defined carbons of the fatty acyl chain. FADS2 and several other genes involved in sebocyte differentiation are induced by dihydrotesterone in human sebocytes expressing the androgen receptor (Barrault et al, 2015)…”

Section: Resultsmentioning

confidence: 99%

Sebaceous Gland Atrophy in Psoriasis: An Explanation for Psoriatic Alopecia?

Rittié

Tejasvi

Harms

et al. 2016

Journal of Investigative Dermatology

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In a transcriptome study of psoriatic (PP) vs. normal (NN) skin, we found a co-expressed gene module (N5) enriched 11.5-fold for lipid biosynthetic genes. We also observed fewer visible hairs in PP skin, compared to uninvolved (PN) or NN skin (p<0.0001). To ask whether these findings might be due to abnormalities of the pilosebaceous unit, we carried out 3D morphometric analysis of paired PP and PN biopsies. Sebaceous glands (SG) were markedly atrophic in PP vs. PN skin (91% average reduction in volume, p=0.031). Module N5 genes were strongly downregulated in PP vs. NN skin (fold-change [FC] < 0.25, 44.4-fold), and strongly up-regulated in sebaceous hyperplasia (SH, FC > 4, 54.1-fold). The intersection of PP-downregulated and SH-upregulated gene lists generated a gene expression signature consisting solely of module N5 genes, whose expression in PP vs. NN skin was inversely correlated with the signature of IL17-stimuated keratinocytes. Despite loss of visible hairs, morphometry identified elongated follicles in PP vs. PN skin (average 1.7 vs. 1.2 μm, p=0.020). These results document SG atrophy in non-scalp psoriasis, identify a cytokine-regulated set of SG signature genes, and suggest that loss of visible hair in PP skin may result from abnormal SG function.

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Section: Resultsmentioning

confidence: 99%

Sebaceous Gland Atrophy in Psoriasis: An Explanation for Psoriatic Alopecia?

Rittié

Tejasvi

Harms

et al. 2016

Journal of Investigative Dermatology

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“…Variations of endogenous androgens may contribute to lower K75 expression as shown in vitro. 32 • Similarly, we could consider to some extent the increased expression of K75 as an in vivo comedone-preventive effect of topical SMFE, recapitulating thereby its in vitro stimulating effect on K75 gene expression. Specifically designed controlled studies would be required to confirm this relationship.…”

Section: Discussionmentioning

confidence: 99%

Microcomedones in non‐lesional acne prone skin New orientations on comedogenesis and its prevention

Fontao

Engelbrechten

Seilaz

et al. 2019

Acad Dermatol Venereol

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Background In non‐lesional skin of acne patients, cyanoacrylate skin surface stripping can harvest a structure called microcomedone (MC) which is the earliest phase of comedogenesis; the root of any subsequent clinical lesion and a target for the prevention of acne relapses. More information is needed on the putative biochemical contributors (biomarkers) of comedogenesis expressed in MC. Methods Proteins expressed in MC were screened by proteomics, immunohistochemistry and Western blotting. The in vitro effects of a comedolytic Silybum marianum fruit extract (SMFE) were studied in sebocyte cultures by RNA‐Seq and modulation of CYP1A1 by qPCR and enzymatic activity. MC severity was correlated to lesions counts and keratin expression during 48 weeks in 23 acne patients using a topical comedolytic formulation containing SMFE. Results Two infundibular keratins, K75 and K79, co‐localized in MC with the sebocyte progenitor cell marker LRIG1 and were used as a biomarker of comedogenesis for the follow‐up of patients. In cultured sebocytes exposed to SMFE (i) transcriptomic analysis showed an up‐regulation by a factor of 15 of RNA coding for K75 and (ii) the gene expression and catalytic activity of CYP1A1 under exposure to dioxin was decreased. In the acne patients using SMFE, the MC index in non‐lesional skin decreased over time and remained until the 48th week, significantly lower than that of the first week. There was a high correlation between the decrease of MC index and the decrease and stability of the clinical lesions counts over time. Importantly, a low MC index status was found to be associated with a significant higher K75 expression in microcomedones. Discussion These observations provide new orientations on the mechanism of comedogenesis and its prevention. Maintaining a low MC status in non‐lesional skin is a sound target for the prevention of acne relapse and a good sentinel of acne remissions.

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“…Antimicrobial role of sebum (innate immunity) SZ95 [58][59][60][61][62][63] SEB-1 [64] Expression and regulation of sebocyte lipid droplet-associated proteins SZ95 [50,[65][66][67] Seb-E6E7 [50] Mechanisms of IGF-1-mediated stimulation of sebaceous lipogenesis SEB-1 [68,69] SZ95 [70] Actions of peroxisome proliferator-activated receptors in sebocytes SEB-1 [71] SZ95 [72][73][74] Actions of endocannabinoids in sebocytes SZ95 [75] Mechanisms of retinoid-mediated inhibition of sebaceous lipogenesis SZ95 [39,76] SEB-1 [77][78][79] Expression of steroidogenesis-related enzymes and regulation of local androgen synthesis SZ95 [40,80] SEB-1 [41] SEBO662 [44] Mechanisms of apoptosis in sebocytes SZ95 [81] SEB-1 [41] Cutaneous functions of the vitamin D system SZ95 [82,83] Regulation of sebaceous lipogenesis by microRNAs SZ95 [49] Neuropeptide synthesis and their action on sebocytes SZ95 [84,85] molecular and cellular processes underlying sebaceous lipogenesis and their perturbation in SG diseases (Table 1). Recent examples of fields pushed forward by employing immortalized human SG cell lines include the analysis of sebocyte adipokines, [48] the identification of microRNAs associated with sebaceous differentiation, [49] and the study of the proteins associated with cytoplasmic SG lipi...…”

Section: Cell Line Referencesmentioning

confidence: 99%

Primary sebocytes and sebaceous gland cell lines for studying sebaceous lipogenesis and sebaceous gland diseases

Schneider

Zouboulis

2018

Experimental Dermatology

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Sebocytes, the major cell type in sebaceous glands, are differentiated epithelial cells that gradually accumulate lipids and eventually disrupt, releasing their content (sebum) in a secretory process known as holocrine secretion. Via the hair canal, sebum reaches the skin surface, where it has several known or postulated functions, including pheromonal, thermoregulatory, antimicrobial and antioxidant activities. Altered sebum secretion and/ or structural sebaceous gland changes have also been involved in the pathogenesis of skin diseases, such as acne vulgaris and some forms of alopecia. Here, we assess how recent work employing primary sebocytes and sebaceous gland cell lines contributed for our understanding of sebaceous lipogenesis and its role in skin health and disease. K E Y W O R D Slipid droplets, lipids, perilipins, sebaceous glands

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Androgens induce sebaceous differentiation in sebocyte cells expressing a stable functional androgen receptor

Cited by 43 publications

References 30 publications

Sebaceous Gland Atrophy in Psoriasis: An Explanation for Psoriatic Alopecia?

Sebaceous Gland Atrophy in Psoriasis: An Explanation for Psoriatic Alopecia?

Microcomedones in non‐lesional acne prone skin New orientations on comedogenesis and its prevention

Primary sebocytes and sebaceous gland cell lines for studying sebaceous lipogenesis and sebaceous gland diseases

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