Study On The Expression Change Of ApoD And AR In The Apocrine Sweat Glands Of Axillary Osmidrosis And The Role Of AP-1 In It

The pathogenesis of axillary osmidrosis is unclear at present.Some research results have showed that the main components of the stink is the E-isomer of 3-methyl-2-hexenoic acid (E-3M2H), while volatile sulfur compounds also a certain proportion. Apolipoprotein D(ApoD) in human apocrine sweat gland is a specific apocrine secretion odor-binding protein(ASOB). It has two forms: ASOB1and ASOB2. ASOB2 plays a major role in the the transport process of odor. Under the influence of Hormones or the external environment, the secretion of E-3M2H and ApoD/ASOB2 increases. E-3M2H Combined with ApoD secretes into the lumens of apocrine sweat gland and transports to the skin surface through the sweat ducts. The secretion which souring with bacteria brokes down and creates pungent odor which Seriously affects the social interaction and mental health of the axillary osmidrosis patients. Studies have shown that JNK signaling pathway is relevant to the pathogenesis of many diseases (including obesity, type 2 diabetes, inflammation, nerve degeneration, and tumors, etc.). However, there is no study on JNK and AP-1(Downstream transcription factor of JNK1) in the pathogenesis of axillary osmidrosis in domestic and overseas areas at present. Our research group previously founded that ApoD expression can be stimulated by AR signaling through JNK1, but Inhibition of JNK1 does not completely block the expression of ApoD which was regulated by AR signal. It suggest ed that AR can also stimulate the expression of ApoD by JNK1 non-dependent manner. Moreover, JNK1 can stimulate the transcriptional activity of AR by itself. It suggested that the expression of ApoD may beby regulated by JNK1 through AR signal. Therefore, we can imagine the existence of a feedback between AR signaling and JNK1 signal. We collected armpit skin tissue samples of axillary osmidrosis group and normal group (all two groups are volunteers), then we detected the content of apolipoprotein D(ApoD) and androgen receptor in apocrine sweat gland through Immunohistochemistry(IHC), Western blotting(WB) and Real-time PCR. Furthermore, we researched the relation between ApoD/AR and odor strength. With the treatment of 5α-DHT joint AP-1 inhibitor(Curcumin ) in cultured sweat gland cells, we investigated the the effect of AP-1(Downstream transcription factor of JNK1) in the pathogenesis of axillary osmidrosis, which provide a theoretical basis and clinical guidance for the prevention, diagnosis and treatment of axillary osmidrosis.Objective:1) The content of ApoD and AR in apocrine sweat gland of axillary osmidrosis group and normal group is detected,and we are to study the expression change and the effect of them in axillary osmidrosis.2) To study the relation of ApoD/AR and odor strength in apocrine sweat gland of axillary osmidrosis,and to confirm the effect in the pathogenesis of axillary osmidrosis.3) On the basis of confirming the relation between ApoD/AR and odor strength and previous experiment of our research group, furthermore, study on the effect of AP-1(Downstream transcription factor of JNK1) in the pathogenesis of axillary osmidrosis can provide a new clinical guidance for the treatment of axillary osmidrosis.Methods:1) We collected armpit skin tissue samples of axillary osmidrosis group and normal group (all two groups are volunteers), then we detected the expression content of ApoD and AR in apocrine sweat gland through Immunohistochemistry, Western blotting and Real-time PCR. Furthermore, we used Image-Pro Plus 5.0 and FluorChem FC2 Analysis system to analyze the results.2) Ordered volunteers who bathed and forbid against eating spicy food the night before. Briefly, the osmidrosis patients were asked to stay in a comfortable environment(with the temperature of 28°C, door closed, indoor cleaned).The volunteers Fully exposed axillary area, three doctors smell armpit odor smell in different distances(1m, 3m and 5m). The extent of the osmidrosis were classified into mild, middle and severe degrees corresponding to the unpleasant odor obviously smelled at 1, 3 and 5 meters distances. Biopsy specimens of the underarm area were obtained from axillary osmidrosis patients. The intact skin from was treatmented, then we detected the content of ApoD and AR through Real-time PCR. Statistical analysis and processing was done later.3) Sweat gland cells culture used the intact skin of underarm area. The activity of AP-1 was inhibited by Curcumin , and the expression change of ApoD was detected by Western blotting and Real-time PCR.Results:1) The expression of ApoD and AR was significantly higher in axillary Osmidrosis than that in normal samples. Expression of ApoD/AR is statistically differernt between two groups.2) There was a linear relationship between the degree of relative expression of ApoD/AR and odor strength(P﹤0.05). The degree of relative expression of ApoD increased With the increase of odor strength.3) Under the inhibition of Curcumin , the expression of ApoD was significantly lower.Conclusions:1) The expression of ApoD and AR was higher in apocrine sweat gland of axillary osmidrosis patients. They may play an important role in the pathogenesis of axillary osmidrosis.2) There was a direct relationship between the degree of relative expression of ApoD/AR and odor strength. It may play a crucial role in the process of axillary osmidrosis odor.3) Curcumin inhibited the activation of AP-1, and the expresstion of ApoD was depressed. The expresstion of ApoD was upregulated by AP-1(Downstream transcription factor of JNK1) in the pathogenesis of axillary osmidrosis.