Premium
Arginase‐2, a miR‐1299 target, enhances pigmentation in melasma by reducing melanosome degradation via senescence‐induced autophagy inhibition
Author(s) -
Kim NanHyung,
Choi SooHyun,
Yi Nayoung,
Lee Tae Ryong,
Lee AiYoung
Publication year - 2017
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12605
Subject(s) - melanosome , autophagy , downregulation and upregulation , tyrosinase , melasma , keratinocyte , senescence , chemistry , arginase , microbiology and biotechnology , epidermis (zoology) , cancer research , melanin , biology , biochemistry , gene , enzyme , genetics , arginine , anatomy , apoptosis , amino acid , in vitro
Summary Expression profiles revealed miR‐1299 downregulation concomitant with arginase‐2 ( ARG 2) upregulation in hyperpigmented skin of melasma patients. Opposite regulation of tyrosinase and PMEL 17 by miR‐1299 and inverse relationship between miR‐1299 and ARG 2 expression denoted a role of miR‐1299 in pigmentation with ARG 2 as a miR‐1299 target. ARG 2 overexpression or knock‐down in keratinocytes, the main source of ARG 2 in epidermis, positively regulated tyrosinase and PMEL 17 protein levels, but not mRNA levels or melanosome transfer. ARG 2 overexpression in keratinocytes reduced autophagy equivalent to 3‐ MA , an autophagy inhibitor which also increased tyrosinase and PMEL 17 protein levels, whereas ARG 2 knock‐down induced opposite results. Autophagy inducer rapamycin reduced ARG 2‐increased tyrosinase and PMEL 17 protein levels. Also, autophagy was reduced in late passage‐induced senescent keratinocytes showing ARG 2 upregulation. ARG 2, but not 3‐ MA , stimulated keratinocyte senescence. These results suggest that ARG 2 reduces autophagy in keratinocytes by stimulating cellular senescence, resulting in skin pigmentation by reducing degradation of transferred melanosomes.