Open AccessCholesterol metabolism plays a crucial role in the regulation of autophagy for cell differentiation of granular convoluted tubules in male mouse submandibular glands
Author(s) -
Akiko Suzuki,
Junbo Shim,
Kenichi Ogata,
Hiroki Yoshioka,
Junichi Iwata
Publication year - 2019
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.754
H-Index - 325
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.178335
Subject(s) - biology , autophagy , medicine , endocrinology , morphogenesis , hormone , transcription factor , salivary gland , androgen , microbiology and biotechnology , sexual differentiation , nuclear receptor , cholesterol , androgen receptor , lipid metabolism , gene , cancer , genetics , biochemistry , apoptosis , prostate cancer
It has been long appreciated that sex-hormone receptors are expressed in various non-gonadal organs. However, it remains unclear how sex hormones regulate the morphogenesis of these non-gonadal organs. To address this question, we used a male mouse model of androgen-dependent salivary gland morphogenesis. Mice with excessive cholesterol synthesis in the salivary glands exhibited defects in the maturation of granular convoluted tubules (GCTs), which is regulated through sex hormone-dependent cascades. We found that excessive cholesterol synthesis resulted in autophagy failure specifically in the duct cells of salivary glands, followed by the accumulation of NRF2, a transcription factor known as one of the specific substrates for autophagy. The accumulated NRF2 suppressed the expression of Foxa1, which forms a transcriptional complex with the androgen receptor to regulate target genes. Taken together, our results indicate that cholesterol metabolism plays a crucial role in GCT differentiation through autophagy.