TY - JOUR
T1 - PLIN2, the major perilipin regulated during sebocyte differentiation, controls sebaceous lipid accumulation in vitro and sebaceous gland size in vivo
AU - Dahlhoff, Maik
AU - Camera, Emanuela
AU - Picardo, Mauro
AU - Zouboulis, Christos C.
AU - Chan, Lawrence
AU - Chang, Benny Hung Junn
AU - Schneider, Marlon R.
N1 - Funding Information:
The authors would like to thanks C. Rose, M.D. (Department of Dermatology, University of Lübeck, Germany), for the human skin biopsy samples, Dr. Matteo Ludovici (Institute of Dermatology San Gallicano, Rome, Italy) for the preparation and LC/MS analysis of SZ95 sebocyte lipid extracts, and Stefanie Riesemann (Gene Center, Munich) for Western blot analysis. E.C., M.P., and M.L. were supported by the Italian Ministry of Health through the grant RF-2010-2316435. L.C. and B.C. were each supported by grants ( HL-51586 and DK-084495 , respectively) from the US National Institutes of Health .
Funding Information:
This work was supported by a grant from the Cicatricial Alopecia Research Foundation to M.R.S.
PY - 2013
Y1 - 2013
N2 - Background Lipid synthesis and storage are accomplished by lipid droplets (LDs). The perilipin family of LD-associated proteins, comprising 5 members (PLIN1-PLIN5), has been well characterized in adipocytes but not in sebocytes, epithelial cells in which LD formation is a key feature of the cellular differentiation. Methods Perilipin expression in the sebaceous gland cell line SZ95 and in human sebaceous glands was studied by qRT-PCR, Western blots, and immunohistochemistry. Lipid accumulation was evaluated by Nile red staining and mass spectrometry. Results PLIN2 and PLIN3 are the most abundant perilipins in undifferentiated sebocytes. Induction of lipogenesis by linoleic acid (LA) resulted in increased transcript levels of all perilipins except for PLIN3 and in a time-dependent increase of PLIN2 protein. Nile red staining revealed that siRNA-mediated downregulation of PLIN2 significantly impaired basal and LA-induced lipid accumulation. Mass spectrometry revealed PLIN2 deficiency to cause a reduction in the amount of several specific lipid fractions, including di- and triacyl-glycerol esters, phosphatidylcholine lipids, and ceramides in sebocytes under basal conditions. In contrast, PLIN2 downregulation exerted a statistically significant inhibitory effect only on the accumulation of specific LA-induced triglycerides. PLIN2-deficient mice showed normal morphology of sebaceous glands. However, their sebaceous glands were significantly reduced in size and showed less cell proliferation. Conclusions PLIN2 is the major perilipin regulated during sebocyte differentiation in vitro. PLIN2 is also important for sebaceous lipid accumulation in vitro and regulates sebaceous gland size in vivo. General significance Our study provides the first systematic analysis of LD-associated proteins in sebocytes.
AB - Background Lipid synthesis and storage are accomplished by lipid droplets (LDs). The perilipin family of LD-associated proteins, comprising 5 members (PLIN1-PLIN5), has been well characterized in adipocytes but not in sebocytes, epithelial cells in which LD formation is a key feature of the cellular differentiation. Methods Perilipin expression in the sebaceous gland cell line SZ95 and in human sebaceous glands was studied by qRT-PCR, Western blots, and immunohistochemistry. Lipid accumulation was evaluated by Nile red staining and mass spectrometry. Results PLIN2 and PLIN3 are the most abundant perilipins in undifferentiated sebocytes. Induction of lipogenesis by linoleic acid (LA) resulted in increased transcript levels of all perilipins except for PLIN3 and in a time-dependent increase of PLIN2 protein. Nile red staining revealed that siRNA-mediated downregulation of PLIN2 significantly impaired basal and LA-induced lipid accumulation. Mass spectrometry revealed PLIN2 deficiency to cause a reduction in the amount of several specific lipid fractions, including di- and triacyl-glycerol esters, phosphatidylcholine lipids, and ceramides in sebocytes under basal conditions. In contrast, PLIN2 downregulation exerted a statistically significant inhibitory effect only on the accumulation of specific LA-induced triglycerides. PLIN2-deficient mice showed normal morphology of sebaceous glands. However, their sebaceous glands were significantly reduced in size and showed less cell proliferation. Conclusions PLIN2 is the major perilipin regulated during sebocyte differentiation in vitro. PLIN2 is also important for sebaceous lipid accumulation in vitro and regulates sebaceous gland size in vivo. General significance Our study provides the first systematic analysis of LD-associated proteins in sebocytes.
KW - Lipid droplets
KW - Perilipins
KW - Sebaceous glands
UR - http://www.scopus.com/inward/record.url?scp=84879482208&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84879482208&partnerID=8YFLogxK
U2 - 10.1016/j.bbagen.2013.05.016
DO - 10.1016/j.bbagen.2013.05.016
M3 - Article
C2 - 23688400
AN - SCOPUS:84879482208
SN - 0304-4165
VL - 1830
SP - 4642
EP - 4649
JO - Biochimica et Biophysica Acta - General Subjects
JF - Biochimica et Biophysica Acta - General Subjects
IS - 10
ER -