The mineralocorticoid receptor plays a transient role in mouse skin development

Abstract

which we previously reported to be a sensitive marker ( Figure S3 and Table S1). We also examined the half-life of SNHG5 in the serum ( Figure S4). ConclusionsSNHG5 is a member of the non-coding multiple small nucleolar RNA host gene family. The SNHG5 gene is 524 bp in size and located on chromosome 6q15 at the breakpoint of chromosomal translocation t(3,6)(q27;q15); this site is involved in human B-cell lymphoma (7). The fact that the serum levels of SNHG5 were upregulated in patients with MM suggests that SNHG5 may play some roles in melanomagenesis and/or melanoma metastasis. In this study, the serum levels of SNHG5 did not increase in the patients with SCC. However, the present results are associated with some limitations due to the small number of patients. To answer the question as to whether SNHG5 is specifically involved in the pathogenesis of MM, further studies using more samples from other cancers are needed. AcknowledgementsThis work was supported by JSPS KAKENHI grant numbers 25870545 and 15K09772. Author contributionsY. I. performed the experiments, analysed the data and wrote the manuscript. S. F. designed the research and wrote the manuscript. A. T., J. Y., A. M. and S. N. contributed to the sampling. W.Z., J. A., I. K. and S. M.performed the experiments. M. J. and H. I. provided excellent scientific suggestion. Conflict of interestThe authors declare no conflict of interests. Supporting InformationAdditional supporting data may be found in the supplementary information of this article.Data S1. The detailed methodologies of the experiments. Figure S1. The relative expression of serum SNHG5 levels in 5 MM patients before operation (pre-operation), after operation (post-operation), and at recurrence (recurrent). P values were determined by a Mann-Whitney test. Figure S2. The relative concentration of tissue SNHG5 in patients with melanoma and those of nevus SNHG5. SNHG5 levels were measured with real-time PCR. The ordinate shows SNHG5 relative concentration. Bars describe median. P values were determined by a Mann-Whitney test. N.S. means not significant. Figure S3. The relative serum mir-221 levels in five MM patients before the operation (preoperation), after the operation (post-operation) and at recurrence (recurrent). P values were determined according to the Mann-Whitney test. Figure S4. The half-life analysis of lncRNA in the serum. The SNHG5 levels in three MM serum samples were mesuared at three points: just after thawing (0 h), after one day at room temperature (24 h) and after three days at room temperature (72 h). The dotted line shows the half-life of SNHG5. Table S1. The list of patients with melanoma showing the pathological stage, age, sex, type of melanoma, relative serum levels of SNHG5 and mir-221 and therapy before sampling. M means male and F means female. The shaded area means their relative expressions are over the cut-off value (the mean + 2SD of normal subjects).

A novel actor in skin biology: the mineralocorticoid receptor

“…Interestingly, the skin phenotype reported by Boix et al is at least partially distinct from that of GR knockout mice, which present with delayed epidermal barrier formation (not achieved by MR knockout), while epidermal hypertrophy is observed both in MR‐ and GR‐null embryos . MR or GR knockout mice do not show evidence for alterations in the density of hair follicles at birth.…”

“…One key question that arose from these pioneering studies was whether these two receptors were essentially functionally redundant in the epidermis, or whether each exerts some specific roles. On this background, the paper of Boix et al extends our knowledge on the role of the epidermal MR through analysis of the skin phenotype of mice with MR knockout.…”

“…Cutaneous glucocorticoid availability also depends on local synthesis ( de novo synthesis from cholesterol) and on local metabolism: they can be inactivated by the enzyme HSD2 (11 beta hydroxysteroid dehydrogenase type 2) or regenerated from inactive glucocorticoids by the enzyme HSD1 (11 beta hydroxysteroid dehydrogenase type 1) . The report of Boix et al is also interesting in that it shows both enzymes to be expressed at much higher levels during skin development than in adult mouse skin, suggesting that they can modulate intra‐cutaneous glucocorticoid concentrations during embryogenesis, thus influencing the activity of MR‐ and/or GR‐dependent signalling.…”

Glucocorticoid Receptor Signaling in Skin Barrier Function

“…In human and mouse skin, HSD11B1 is highly expressed in the epidermis and dermis, with higher levels in differentiating keratinocytes [29,36]. HSD11B2 has been also detected in the suprabasal epidermis of human and developing mouse skin as well as in sweat glands, an important target for aldosterone-mineralocorticoid receptor regulation [37][38][39][40].…”

Mineralocorticoid Receptor Antagonists—A New Sprinkle of Salt and Youth

“…Attempts at defining a distinct physiological role for MR in skin were first made using a conditional mouse model in which targeted expression of MR was directed by the use of a keratinocyte specific promoter (K5-MR mice), which ultimately yielded a phenotype reminiscent of GCinduced epidermal atrophy (Sainte Marie et al, 2007). In contrast, more recent knockout mouse models have demonstrated that MR-KO embryos display epidermal hyperplasia (Boix et al, 2016).…”