The role of NPY2R/NFATc1/DYRK1A regulatory axis in sebaceous glands for sebum synthesis.

BACKGROUND: Sebaceous glands (SGs) synthesize and secret sebum to protect and moisturize the dermal system via the complicated endocrine modulation. Dysfunction of SG are usually implicated in a number of dermal and inflammatory diseases. However, the molecular mechanism behind the differentiation, development and proliferation of SGs is far away to fully understand. METHODS: Herein, the rat volar and mammary tissues with abundant SGs from female SD rats with (post-natal day (PND)-35) and without puberty onset (PND-25) were arrested, and conducted RNA sequencing. The protein complex of Neuropeptide Y receptor Y2 (NPY2R)/NPY5R/Nuclear factor of activated T cells 1 (NFATc1) was performed by immunoprecipitation, mass spectrum and gel filtration. Genome-wide occupancy of NFATc1 was measured by chromatin immunoprecipitation sequencing. Target proteins' expression and localization was detected by western blot and immunofluorescence. RESULTS: NPY2R gene was significantly up-regulated in volar and mammary SGs of PND-25. A special protein complex of NPY2R/NPY5R/NFATc1 in PND-25. NFATc1 was dephosphorylated and activated, then localized into nucleus to exert as a transcription factor in volar SGs of PND-35. NFATc1 was especially binding at enhancer regions to facilitate the distal SG and sebum related genes' transcription. Dual specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) contributed to NFATc1 phosphorylation in PND-25, and inactivated of DYRK1A resulted in NFATc1 dephosphorylation and nuclear localization in PND-35. CONCLUSIONS: Our findings unmask the new role of NPY2R/NFATc1/DYRK1A in pubertal SG, and are of benefit to advanced understanding the molecular mechanism of SGs' function after puberty, and provide some theoretical basis for the treatment of acne vulgaris from the perspective of hormone regulation.

Localization of glossopharyngeal obstruction using nasopharyngeal tube versus Friedman tongue position classification in obstructive sleep apnea hypopnea syndrome.

Assessing the severity of glossopharyngeal obstruction is important for the diagnosis and therapy of obstructive sleep apnea hypopnea syndrome (OSAHS). The polysomnography (PSG) with nasopharyngeal tube insertion (NPT-PSG) has shown good results in assessing glossopharyngeal obstruction. The objective of this study was to compare NPT-PSG with Friedman tongue position (FTP) classification which was also used to evaluate the glossopharyngeal obstruction. One hundred and five patients with OSAHS diagnosed by PSG were included in the study. All the patients were successfully examined by NPT-PSG. Based on the grade of FTP classification, 105 patients were divided into four groups. The differences of the general clinical data, PSG and NPT-PSG results were analyzed among the four groups. And the coincidence of diagnosing glossopharyngeal obstruction of two methods was calculated. There was no significant difference among the four groups in general clinical data and PSG results. However, NPT-PSG results were significantly different among the four groups. Following with the increasing FTP, apnea hypopnea index increased and lowest saturation of blood oxygen decreased. There were 38 patients with and other 38 patients without glossopharyngeal obstruction diagnosed by both methods. The coincidence of two methods was 72.4 %. NPT-PSG is an easy and effective method in assessing the severity of glossopharyngeal obstruction. The coincidence between the NPT-PSG and FTP classification is good. But in some special OSAHS patients such as glossoptosis, unsuccessful uvulopalatopharyngoplasty or suspicious pachyglossia, NPT-PSG is better than FTP classification.

Inhalation of hydrogen gas attenuates ouabain-induced auditory neuropathy in gerbils.

AIM: Auditory neuropathy (AN) is a hearing disorder characterized by abnormal auditory nerve function with preservation of normal cochlear hair cells. This study was designed to investigate whether treatment with molecular hydrogen (H(2)), which can remedy damage in various organs via reducing oxidative stress, inflammation and apoptosis, is beneficial to ouabain-induced AN in gerbils. METHODS: AN model was made by local application of ouabain (1 mmol/L, 20 mL) to the round window membrane in male Mongolian gerbils. H(2) treatment was given twice by exposing the animals to H(2) (1%, 2%, and 4%) for 60 min at 1 h and 6 h after ouabain application. Before and 7 d after ouabain application, the hearing status of the animals was evaluated using the auditory brainstem response (ABR) approach, the hear cell function was evaluated with distortion product otoacoustic emissions (DPOAE). Seven days after ouabain application, the changes in the cochleae, especially the spiral ganglion neurons (SGNs), were morphologically studied. TUNEL staining and immunofluorescent staining for activated caspase-3 were used to assess the apoptosis of SGNs. RESULTS: Treatment with H(2) (2% and 4%) markedly attenuated the click and tone burst-evoked ABR threshold shift at 4, 8, and 16 kHz in ouabain-exposed animals. Neither local ouabain application, nor H(2) treatment changed the amplitude of DPOAE at 4, 8, and 16 kHz. Morphological study showed that treatment with H(2) (2%) significantly alleviated SGN damage and attenuated the loss of SGN density for each turn of cochlea in ouabain-exposed animals. Furthermore, ouabain caused significantly higher numbers of apoptotic SGNs in the cochlea, which was significantly attenuated by the H(2) treatment. However, ouabain did not change the morphology of cochlear hair cells. CONCLUSION: The results demonstrate that H(2) treatment is beneficial to ouabain-induced AN via reducing apoptosis. Thus, H(2) might be a potential agent for treating hearing impairment in AN patients.

Dynamic changes in microRNA expression during differentiation of rat cochlear progenitor cells in vitro.

OBJECTIVE: Cochlear progenitor cells could be used to explore the cochlea developmental mechanism and for cell replacement therapy in deafness. MicroRNAs are small, noncoding RNAs that could regulate the cell fate of stem cells, as well as cellular proliferation, differentiation and maturation. An expression profile analysis of microRNAs is necessary to understand their complex roles in differentiating cochlear progenitor cells. METHODS: The microRNAs microarray was used to analyze microRNA expression changes while differentiating cochlear progenitor cells. Quantitative real-time polymerase chain reaction was used to confirm and compare the results of the microarray and to detect the expression pattern of several microRNAs during the differentiation of neural stem cells. RESULTS: Nearly 100 microRNAs were identified from the microarray. Most showed changes in expression levels as cochlear progenitor cell differentiation progressed. The quantitative real-time polymerase chain reaction result demonstrated that the miR-183 family exhibits cell-specific expression in cochlear progenitor cells compared with neural stem cells. CONCLUSIONS: The temporal regulation of these microRNAs indicated that they might play different roles in differentiating cochlear progenitor cells, and that specific microRNAs might influence the cell fate determination of cochlear progenitor cells.

Protective role of hydrogen sulfide against noise-induced cochlear damage: a chronic intracochlear infusion model.

BACKGROUND: A reduction in cochlear blood flow plays an essential role in noise-induced hearing loss (NIHL). The timely regulation of cochlear perfusion determines the progression and prognosis of NIHL. Hydrogen sulfide (H(2)S) has attracted increasing interest as a vasodilator in cardiovascular systems. This study identified the role of H(2)S in cochlear blood flow regulation and noise protection. METHODOLOGY/PRINCIPAL FINDINGS: The gene and protein expression of the H(2)S synthetase cystathionine-γ-lyase (CSE) in the rat cochlea was examined using immunofluorescence and real-time PCR. Cochlear CSE mRNA levels varied according to the duration of noise exposure. A chronic intracochlear infusion model was built and artificial perilymph (AP), NaHS or DL-propargylglycine (PPG) were locally administered. Local sodium hydrosulfide (NaHS) significantly increased cochlear perfusion post-noise exposure. Cochlear morphological damage and hearing loss were alleviated in the NaHS group as measured by conventional auditory brainstem response (ABR), cochlear scanning electron microscope (SEM) and outer hair cell (OHC) count. The highest percentage of OHC loss occurred in the PPG group. CONCLUSIONS/SIGNIFICANCE: Our results suggest that H(2)S plays an important role in the regulation of cochlear blood flow and the protection against noise. Further studies may identify a new preventive and therapeutic perspective on NIHL and other blood supply-related inner ear diseases.

A comparison of the proliferative capacity and ultrastructure of proliferative cells from the cochleae of newborn rats of different ages.

OBJECTIVE: Recent reports have shown that multipotent stem cells/progenitor cells that are capable of proliferation and regeneration are present in mammalian cochleae. However, progenitor cells have not been isolated from the adult cochlea. We examined the proliferative potential of cells derived from neonatal rats of various ages. The determination of the differences between the proliferative cells from rats of different ages may provide clues to the mechanisms controlling the destiny of these cells. METHODS: Proliferative cells were isolated from the cochleae of 1-, 7-, and 14-day-old rats, and the proliferative capacity and ultrastructure of the cells from each age group were assessed using flow cytometry and transmission electron microscopy, respectively. RESULTS: During the first two postnatal weeks, the number of proliferative cells gradually fell to zero. This decrease occurred in parallel with the impairment of the proliferative capacity of the cells and the accumulation of proliferative cells in G0/G1. In addition, some of the cells exited the cell cycle by means of gradual maturity and apoptosis. CONCLUSIONS: Our study suggests that cochlear proliferative cells are remnants of the progenitor cells that originally gave rise to the sensory epithelium. The disappearance of the cochlear proliferative cells in adult mammalian cochleae may result from their differentiation and/or apoptosis.