Expression of Protease-Activated Receptor-2 in SZ95 Sebocytes and its Role in Sebaceous Lipogenesis, Inflammation, and Innate Immunity

Sang E. Lee, Ji Min Kim, Se K. Jeong, Eung Ho Choi, Christos C. Zouboulis, Seung H. Lee

Research output: Contribution to journalArticle

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Abstract

Protease-activated receptor-2 (PAR-2) functions as innate biosensor for proteases and regulates numerous functions of the skin. However, the expression and physiological role of PAR-2 in sebocytes remain to be elucidated. Here, we identified PAR-2 expression in SZ95 sebocytes at both mRNA and protein levels. Intracellular Ca 2+ mobilization by PAR-2 agonist peptide (PAR-2 AP) or Propionibacterium acnes (P. acnes) culture supernatant was detected, indicating that P. acnes is a potent activator of PAR-2 on sebocytes. The small interfering RNA (siRNA)-mediated PAR-2 knockdown in sebocytes resulted in defective differentiation and lipogenesis. PAR-2 AP treatment enhanced lipogenesis and sterol response element-binding protein-1 (SREBP-1) expression, suggesting a role of PAR-2 in the differentiation and lipogenesis of sebocytes. Moreover, PAR-2 AP induced cytokines and human β-defensin-2 (hBD-2) transcription in sebocytes. PAR-2 expression was increased in sebaceous glands of acne lesions. PAR-2 silencing by siRNA abrogated the increase in sebaceous lipogenesis and SREBP-1 expression by P. acnes supernatant. PAR-2 knockdown also inhibited the P. acnes supernatant-induced expression of cytokines and hBD-2. In conclusion, PAR-2 is expressed in SZ95 sebocytes and mediates differentiation, lipogenesis, inflammation, and innate immunity in response to P. acnes. Therefore, PAR-2 might be a therapeutic target for sebaceous gland disorders such as acne.

Original languageEnglish
Pages (from-to)2219-2227
Number of pages9
JournalJournal of Investigative Dermatology
Volume135
Issue number9
DOIs
Publication statusPublished - 2015 Sep 18

Fingerprint

PAR-2 Receptor
Lipogenesis
Innate Immunity
Inflammation
Propionibacterium acnes
Sebaceous Glands
Acne Vulgaris
Response Elements
Sterols
Small Interfering RNA
Carrier Proteins
Cytokines
Defensins
Biosensing Techniques
Transcription

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Lee, Sang E. ; Kim, Ji Min ; Jeong, Se K. ; Choi, Eung Ho ; Zouboulis, Christos C. ; Lee, Seung H. / Expression of Protease-Activated Receptor-2 in SZ95 Sebocytes and its Role in Sebaceous Lipogenesis, Inflammation, and Innate Immunity. In: Journal of Investigative Dermatology. 2015 ; Vol. 135, No. 9. pp. 2219-2227.
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abstract = "Protease-activated receptor-2 (PAR-2) functions as innate biosensor for proteases and regulates numerous functions of the skin. However, the expression and physiological role of PAR-2 in sebocytes remain to be elucidated. Here, we identified PAR-2 expression in SZ95 sebocytes at both mRNA and protein levels. Intracellular Ca 2+ mobilization by PAR-2 agonist peptide (PAR-2 AP) or Propionibacterium acnes (P. acnes) culture supernatant was detected, indicating that P. acnes is a potent activator of PAR-2 on sebocytes. The small interfering RNA (siRNA)-mediated PAR-2 knockdown in sebocytes resulted in defective differentiation and lipogenesis. PAR-2 AP treatment enhanced lipogenesis and sterol response element-binding protein-1 (SREBP-1) expression, suggesting a role of PAR-2 in the differentiation and lipogenesis of sebocytes. Moreover, PAR-2 AP induced cytokines and human β-defensin-2 (hBD-2) transcription in sebocytes. PAR-2 expression was increased in sebaceous glands of acne lesions. PAR-2 silencing by siRNA abrogated the increase in sebaceous lipogenesis and SREBP-1 expression by P. acnes supernatant. PAR-2 knockdown also inhibited the P. acnes supernatant-induced expression of cytokines and hBD-2. In conclusion, PAR-2 is expressed in SZ95 sebocytes and mediates differentiation, lipogenesis, inflammation, and innate immunity in response to P. acnes. Therefore, PAR-2 might be a therapeutic target for sebaceous gland disorders such as acne.",
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Expression of Protease-Activated Receptor-2 in SZ95 Sebocytes and its Role in Sebaceous Lipogenesis, Inflammation, and Innate Immunity. / Lee, Sang E.; Kim, Ji Min; Jeong, Se K.; Choi, Eung Ho; Zouboulis, Christos C.; Lee, Seung H.

In: Journal of Investigative Dermatology, Vol. 135, No. 9, 18.09.2015, p. 2219-2227.

Research output: Contribution to journalArticle

TY - JOUR

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AU - Lee, Sang E.

AU - Kim, Ji Min

AU - Jeong, Se K.

AU - Choi, Eung Ho

AU - Zouboulis, Christos C.

AU - Lee, Seung H.

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