Autophagy protects murine preputial glands against premature aging, and controls their sebum phospholipid and pheromone profile
| العنوان: | Autophagy protects murine preputial glands against premature aging, and controls their sebum phospholipid and pheromone profile |
|---|---|
| المؤلفون: | Samuele Zoratto, Maria Buchberger, Michaela Sochorová, Barbara Lengauer, Bahar Golabi, Florian Gruber, Leopold Eckhart, Dragan Copic, Christopher Kremslehner, Heidemarie Rossiter, Martin Direder, Michael Mildner, Erwin Tschachler, Ionela-Mariana Nagelreiter, Martina Marchetti-Deschmann, Supawadee Sukseree, Veronika Mlitz |
| المصدر: | Autophagy |
| بيانات النشر: | Informa UK Limited, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Sebaceous gland, Perilipin 2, Preputial gland, Phospholipid, Phosphatidylserines, Perilipin-2, Pheromones, Mice, chemistry.chemical_compound, Lipid droplet, Autophagy, medicine, Animals, Molecular Biology, Phospholipids, Phosphatidylethanolamine, biology, Holocrine, Aging, Premature, Lipid metabolism, Cell Biology, Cell biology, Sebum, medicine.anatomical_structure, chemistry, biology.protein, lipids (amino acids, peptides, and proteins), Research Paper |
| الوصف: | Preputial glands are large lipid and hormone secreting sebaceous organs of mice, and present a convenient model for the investigation of biological processes in sebocytes. Suppression of ATG7-dependent macroautophagy/autophagy in epithelial cells of murine skin causes enlargement of hair follicle-associated sebaceous glands and alters the lipid profile of sebum. We have now extended these studies to the preputial glands and find that autophagy significantly delays the onset of age-related ductal ectasia, influences lipid droplet morphology and contributes to the complete dissolution of the mature sebocytes during holocrine secretion. Single cell RNA sequencing showed that many genes involved in lipid metabolism and oxidative stress response were downregulated in immature and mature epithelial cells of ATG7-deficient glands. When analyzing the lipid composition of control and mutant glands, we found that levels of all phospholipid classes, except choline plasmalogen, were decreased in the mutant glands, with a concomitant accumulation of diacyl glycerides. Mass spectrometric imaging (MSI) demonstrated that phospholipid species, specifically the dominant phosphatidylcholine (PC 34:1), were decreased in immature and mature sebocytes. In addition, we found a strong reduction in the amounts of the pheromone, palmityl acetate. Thus, autophagy in the preputial gland is not only important for homeostasis of the gland as a whole and an orderly breakdown of cells during holocrine secretion, but also regulates phospholipid and fatty acid metabolism, as well as pheromone production. ABBREVIATIONS: ATG7: autophagy related 7; BODIPY: boron dipyrromethene; DAG: diacyl glycerides; DBI: diazepam binding inhibitor; GFP: green fluorescent protein; KRT14: keratin 14; HPLC-MS: high performance liquid chromatography-mass spectrometry; LD: lipid droplet; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MSI: mass spectrometric imaging; ORO: Oil Red O; PC: phosphatidylcholine; PE: phosphatidylethanolamine; PG: preputial gland; PLIN2: perilipin 2; PtdIns: phosphatidylinositol; PL: phospholipids; POPC: 1-palmitoyl-2-oleoyl-PC; PS: phosphatidylserine; qRT-PCR: quantitative reverse transcribed PCR; SG: sebaceous gland; scRNAseq: single-cell RNA sequencing; TAG: triacylglycerides; TLC: thin layer chromatography. |
| تدمد: | 1554-8635 1554-8627 |
| DOI: | 10.1080/15548627.2021.1966716 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ee0152a7bddb1fc76bf47a079e6814d6 https://doi.org/10.1080/15548627.2021.1966716 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ee0152a7bddb1fc76bf47a079e6814d6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15548635 15548627 |
|---|---|
| DOI: | 10.1080/15548627.2021.1966716 |