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Rac -dependent signaling from keratinocytes promotes differentiation of intradermal white adipocytes

ABSTRACT: Rac signaling affects numerous downstream targets; however, few studies have established in vivo levels using model animals. In the present study, wWe generated mice with a single knockout (KO) of Rac1 (Keratin5 (K5)-Cre;Rac1flox/flox, hereafter Rac1-KO) and double KO of Rac1 and Rac3 (K5-Cre;Rac1flox/flox;Rac3−/−, hereafter Rac1/Rac3-DKO) in keratinocytes. Hairless phenotype in Rac1-KO mice was markedly exacerbated in Rac1/Rac3-DKO mice. Notably, Rac1-KO mice also exhibited thinner dermal white adipose tissue, which was considerably further reduced in Rac1/Rac3-DKO mice. DNA microarray using primary keratinocytes from Rac1/Rac3-DKO mice exhibited decreased mRNA levels of Bmp2, Bmp5, Fgf20, Fgf21, Fgfbp1, and Pdgf-alpha. Combinational treatment with BMP2 and FGF21, BMP2 and FGF20, or PDGF and FGF21 in culture medium, but not individual purified recombinant proteins, could differentiate 3T3-L1 fibroblasts into adipocytes, as could culture media obtained from primary keratinocytes (both human and mouse). Conversely, addition of anti-BMP2 or anti-FGF21 antibodies into the culture medium inhibited fibroblast differentiation. Furthermore, combinational treatment with BMP2 and FGF21 promoted adipocyte differentiation only of rat primary white adipocyte precursors but not rat primary brown adipocyte precursors. Notably, brown adipogenesis by FGF21 was inhibited by BMP2. Thus, we here proposed a novel paracrine pathway from keratinocytes to intradermal pre-adipocytes using Rac1/Rac3-DKO mice, which is Rac-dependent and functions as an inducer of white adipocytes.

ORGANISM(S): Mus musculus

PROVIDER: GSE122234 | GEO | 2019/11/06

REPOSITORIES: GEO

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