title: Augmentation of gene expression and production of promatrix metalloproteinase 2 by Propionibacterium acnes-derived factors in hamster sebocytes and dermal fibroblasts: a possible mechanism for acne scarring.
abstract: Aberrant extracellular matrix (ECM) remodeling in sebaceous glands and pilosebaceous units in the skin is associated with scar formation under acne conditions. To investigate the involvement of Propionibacterium acnes (P. acnes), a Gram-positive anaerobic microbial species, in ECM remodeling in sebaceous glands and pilosebaceous units, we examined the effects of P. acnes culture media, formalin-fixed P. acnes, and peptidoglycan (PGN) from Gram-positive bacteria walls on the production of promatrix metalloproteinase 2 (proMMP-2)/progelatinase A in hamster sebocytes and dermal fibroblasts. When hamster sebocytes (1.8×10(5) cells) and dermal fibroblasts (1×10(5) cells) were treated with P. acnes culture media and formalin-fixed P. acnes (corresponding to 1×10(6) and 1×10(7) bacterial cells), the production of proMMP-2 was augmented. In addition, PGN (5-50 µg/ml) dose-dependently augmented the production of proMMP-2 in both cells. Furthermore, the PGN (50 µg/ml)-augmented proMMP-2 production was resulted from an increase of its transcript. In contrast, there were no changes in cell proliferative activity in either the P. acnes or PGN-treated sebocytes and dermal fibroblasts, indicating that the augmented proMMP-2 production was not due to an increase in cell numbers. Therefore, these results provide novel evidence that PGN transcriptionally up-regulates the production of proMMP-2 in hamster sebocytes and dermal fibroblasts. Given an increase in the quantity of Gram-positive bacteria, including P. acnes in acne lesions, the aberrant ECM degradation may progress in sebaceous glands and pilosebaceous units, which is associated with acne scar formation.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432–1 Horinouchi, Hachioji, Tokyo 192–0392, Japan. satotak@toyaku.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Sato
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kurihara
authors.forename: Noriko
authors.initials: N
authors.lastname: Akimoto
authors.forename: Norihisa
authors.initials: N
authors.lastname: Noguchi
authors.forename: Masanori
authors.initials: M
authors.lastname: Sasatsu
authors.forename: Akira
authors.initials: A
authors.lastname: Ito
mesh_terms: D000152:Acne Vulgaris / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D000818:Animals; D002473:Cell Wall / Q000737:chemistry; D002921:Cicatrix / Q000209:etiology*; D006224:Cricetinae; D004792:Enzyme Precursors / Q000096:biosynthesis; D005109:Extracellular Matrix / Q000378:metabolism / Q000382:microbiology; D005347:Fibroblasts / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D018093:Gelatinases / Q000096:biosynthesis; D015870:Gene Expression / Q000187:drug effects*; D016908:Gram-Positive Bacterial Infections / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics; D010457:Peptidoglycan / Q000494:pharmacology*; D011425:Propionibacterium acnes / Q000737:chemistry*; D012627:Sebaceous Glands / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D012867:Skin / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D004792:Enzyme Precursors; D010457:Peptidoglycan; D018093:Gelatinases; C069860:progelatinase; D020778:Matrix Metalloproteinase 2