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Pulmonary fibrosis (PF) is a pathological change caused by repeated injuries and repair dysfunction of the alveolar epithelium. Our previous study revealed that the residues Asn3 and Asn4 of peptide DR8 (DHNNPQIR-NH2) could be modified to improve stability and antifibrotic activity, and the unnatural hydrophobic amino acids α-(4-pentenyl)-Ala and d-Ala were considered in this study. DR3penA (DHα-(4-pentenyl)-ANPQIR-NH2) was verified to have a longer half-life in serum and to significantly inhibit oxidative damage, epithelial-mesenchymal transition (EMT) and fibrogenesis in vitro and in vivo. Moreover, DR3penA has a dosage advantage over pirfenidone through the conversion of drug bioavailability under different routes of administration. A mechanistic study revealed that DR3penA increased the expression of aquaporin 5 (AQP5) by inhibiting the upregulation of miR-23b-5p and the mitogen-activated protein kinase (MAPK) pathway, indicating that DR3penA may alleviate PF by regulating MAPK/miR-23b-5p/AQP5. Safety evaluation showed that DR3penA is a peptide drug without obvious toxicity or acute side effects and has significantly improved safety compared to DR8. Thus, our findings suggest that DR3penA, as a novel and low-toxic peptide, has the potential to be a leading compound for PF therapy, which provides a foundation for the development of peptide drugs for fibrosis-related diseases.
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ObjectiveTo investigate the effects of Huashi Runzao prescription （HRP） on the histopathological injury and function of submandibular gland in naive non-obese diabetic （NOD/Ltj） mouse model of Sjögren's syndrome （SS） and its regulatory effect on aquaporin 5 （AQP5） expression in submandibular gland cells. MethodThe SS model was induced in NOD/Ltj mice. The NOD/Ltj female mice aged nine weeks were selected and randomly assigned into model group，HRP group （7.15 g·kg-1·d-1），and hydroxychloroquine （HCQ） group （1.30 g·kg-1·d-1）， and female BALB/c mice in the same age were selected and assigned into the normal group， with six mice in each group. Drug intervention lasted eight weeks. The water consumption and salivary flow rate （SFR） of each group were recorded. The pathological staining results of the submandibular gland of mice in each group were observed and scored. AQP5 expression was determined by immunohistochemistry （IHC） and Western blot. ResultCompared with the normal group， the model group showed increased water consumption （P<0.05） and reduced SFR （P<0.05）. Compared with the model group， the HRP group showed decreased water consumption （P<0.05） and increased SFR （P<0.05）， and the HCQ group showed increased SFR （P<0.05）. In terms of histopathological results of the submandibular gland，compared with the normal group，the model group showed increased pathological score， number of lymphocyte infiltration foci，and percentage of lymphatic infiltration area （P<0.05）. Compared with the model group， the HRP group showed reduced pathological scores and number of lymphocyte infiltration foci （P<0.05）， and the HRP group and the HCQ group showed reduced percentage of lymphatic infiltration area（P<0.05）. The results of IHC and Western blot showed that compared with the normal group，the model group showed down-regulated expression level of AQP5 protein （P<0.05）， and compared with the model group and the HCQ group，the HRP group showed up-regulated expression level of AQP5 protein （P<0.05）. ConclusionHRP can improve the secretion function of submandibular gland acinous cells and glandular structure injury in SS model mice， and its mechanism may be related to the up-regulation of AQP5 protein expression level in submandibular gland cells.
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@#AIM: To observe the protective effect of Qishen recipe on corneal epithelial cells induced by hypertonic fluid, and elucidated its mechanism of action in the treatment of dry eye base on JNK1 / AQP5 pathway.<p>METHODS: Human corneal epithelial cells(HCECs)model was created by osmotic pressure at a concentration of 500mOsm/L for 24h. Serum of rats containing drugs in the blank group, model group, Western medicine group, and Qishen recipe low-dose, medium-dose and high-dose groups were treated on the modeled DE HCECs, and the effects of different drug stimulation on the survival rate of HCECs were tested by CCK-8 method. The expressions of inflammatory factors TNF-α, IL-6 in extracellular fluid were explored by ELISA. The expression of apoptosis factors caspase 1 and AQP5 were detected by immunocytochemistry(ICC). The expressions of AQP5, JNK1, p-JNK1 of HCECs after intervention with different drug concentrations were found by Western blotting.<p>RESULTS: Compared with the blank group, the survival rate of HCECs in each group was significantly reduced(<i>P</i><0.01). The extracellular fluid inflammatory factors TNF-α, IL-6 and caspase-1, p-JNK1, AQP5 protein expression levels increased significantly in each group(all <i>P</i><0.01); In comparison to the model group, the survival rate of HCECs in each medication group increased significantly(all <i>P</i><0.01). The expression levels of TNF-α, IL-6 in the extracellular fluid of each drug group, AQP 5 and p-JNK1 protein expression in HCECs, and the expression of caspase-1 and AQP5 protein in the western medicine group and the Qishen recipe high and medium dose group were all reduced(all <i>P</i><0.05). Compared with the western medicine group, the survival rate of HCECs in the Qishen prescription high-dose group was significantly increased(<i>P</i><0.01). The expression levels of TNF-α and IL-6 in each dose group of Qishen recipe were reduced(all <i>P</i><0.05), while the expression levels of caspase-1 in the high-dose Qishen recipe group and the AQP5 protein expression levels of the high and medium-dose Qishen recipe group saw a decrease(all <i>P</i><0.05). However, there was no statistically significant difference in the JNK1 protein expression of HCECs of all the groups detected by Western blotting method(<i>P</i>>0.05). <p>CONCLUSION: Qishen recipe can not only reduce the JNK1 phosphorylation and AQP5 protein expression of HCECs induced by hypertonicity, but also reduce the expression of inflammatory factors TNF-α, IL-6 and the apoptotic factor caspase-1 of HCECs in the extracellular fluid, thus effectively Inhibit inflammation and apoptosis.
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Objective:To elucidate the effect of miR-182 on proliferation, invasionof endometrial glandular epithelial cells in endometrrosis (EMs) mice via Wnt signaling pathway through targeting Aquaporin5 (AQP5) .Methods:The mice model of EMs were established. Subsequently the adenoepithelial tissue of endometrium were collected and the expression of miR-182 and AQP5 in tissue was detected. Enzyme-linked immunosorbent assay (ELISA) was performed to test the expression of inflammatory factors in normal and EMs mice. Then endometrial glandular epithelial cells in mice were isolated and divided into different groups. qRT-PCR and Western blot was performed to detect the expression of miR-182, AQP5,and Wnt pathway related factors (Wnt-1, β-catenin) in cells. The proliferation activity and invasion ability in each group of cells were examined by MTT and Transwell.Results:Compared with Normal mice, the expression of miR-182 was decreased while AQP5 and Wnt pathway related factors (Wnt-1, β-catenin) expression were increased in endometrial glandular epithelial tissues of EMs mice (all P<0.05) . In cell experiments, miR-182 overexpression or AQP5 silencing could inhibit the expression of Wnt pathway related factors (Wnt-1, β-catenin) . At the same time, cell viability as well as invasion ability were decreased (all P<0.05) . Indexes in miR-182 inhibitor group exhibited an opposite trend compared with that in miR-182 mimic group. The effects of sh-AQP5 on EMs cells could be offset by miR-182 inhibitor. Conclusion:Up-regulated expression of miR-182 can reduce the proliferation and invasion of endometrial glandular epithelial cells of EMs mice through inhibiting the activation of Wnt signaling pathway by down-regulating AQP5.
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The epidermis, the outermost layer of the skin, is the first barrier that comes into contact with the external environment. It plays an important role in resisting the invasion of harmful substances and microbial infections. The skin changes with age and external environmental factors. This study aimed to investigate epidermal stem cells during the process of aging. This study enrolled 9 volunteers with benign pigmented nevus for clinical dermatologic surgery. The phenotypes associated with skin aging changes such as skin wrinkles and elasticity of the unexposed/healthy parts near benign pigmented skin were measured, and epidermal stem cells from this region were isolated for transcriptome sequencing. The results showed that epidermal stem cells could be obtained by magnetic activated cell sorting (MACS) with high purity. Results of the transcriptome sequencing revealed that aquaporin (AQP)5 significantly decreased in the epidermal stem cells with age, and further functional experiments revealed that AQP5 could promote the proliferation and dedifferentiation of HaCaT, but did not influence cell apoptosis. In summary, AQP5 regulated the proliferation and differentiation of epidermal stem cells in skin aging, and it may play an important role in the balance of proliferation and differentiation. However, further studies are needed to determine the mechanism by which AQP5 regulates the proliferation and differentiation of epidermal skin cells in aging.
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Humans , Skin Aging , Aquaporin 5/metabolism , Stem Cells , Cell Differentiation , Cell Proliferation , EpidermisABSTRACT
In many ways, cancer cells are different from healthy cells. A lot of tactical nano-based drug delivery systems are based on the difference between cancer and healthy cells. Currently, nanotechnology-based delivery systems are the most promising tool to deliver DNA-based products to cancer cells. This review aims to highlight the latest development in the lipids and polymeric nanocarrier for siRNA delivery to the cancer cells. It also provides the necessary information about siRNA development and its mechanism of action. Overall, this review gives us a clear picture of lipid and polymer-based drug delivery systems, which in the future could form the base to translate the basic siRNA biology into siRNA-based cancer therapies.
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Alcohol intake is known to affect various organs in the human body, causing reduction of salivation in the oral cavity. Hypo-salivation effect of alcohol is a common feature, but the mechanism in salivary glands is still poorly studied. Therefore, in this study, the changes in salivary secretion and water channel protein (aquaporin5, AQP5) in salivary glands of mice were investigated after ethanol administration. Animals were divided in to 4 groups with the control, 4 g/kg ethanol, 8 g/kg ethanol and 16 g/kg ethanol administration groups. One hour after ethanol administration, saliva was collected from the oral cavity, and the animals were killed and parotid and submandibular glands were extracted to analyze the histopathology, AQP5 immunihistochemistry and AQP5 protein level. According to the results, the salivation rate decreased irrespective of the ethanol dose in mice, and viscosities increased with increase in ethanol dose. However, there were no pathological changes in parotid and submandibular glands due to ethanol administration. Expression of AQP5 in parotid and submandibular glands decreased with increase ethanol administration These results indicate that the reduction of salivary secretion due to acute alcohol intake is closely related to decrease of the water channel protein such as AQP5 in parotid glands and submandibular glands, rather than the damage of salivary glands.
Subject(s)
Animals , Mice , Aquaporin 5 , Eating , Ethanol , Human Body , Mouth , Parotid Gland , Saliva , Salivary Glands , Salivation , Submandibular Gland , Viscosity , WaterABSTRACT
Objective To determine if aquaporin1 ( AQP1) and aquaporin5 ( AQP5) are expressed in the alveolar-capillary membrane in rats, and to investigate the changes of AQP1 and AQP5 expression in the rat with acute lung injury.Methods The distribution of AQP1 and AQP5 in alveolar capillary membrane was investigated by immunohistochemistry and immunoelectron microscopy with affinity-purified antibodies to human AQP1 and AQP5.The possibility that alveolar capillary membrane AQP1 and AQP5 undergo altered regulation was studied by a rat model established using intra-tracheal instillation of lipopolysaccharide (LPS).Results Immunolabelling showed that AQP1 was stained primarily in the microvascular endothelium of normal lungs, while AQP5 was expressed in type I pneumocytes. Immunohistochemical analysis showed a significant decrease in the expression of AQP1 and AQP5 in injured lungs at 4 -48 h after LPS instillation.AQP1 protein was resumed partly at 24 h after LPS instillation and steroid administration, whereas AQP5 was unchanged.Conclusions The decreased expressions of AQP1 and AQP5 in injured lungs suggest that both of them may play a role in abnormal fluid transportation.
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Objective To determine the relationship of the expression of aquaporin 5 (AQP5)with clinicopathology and prognosis of colorectal cancer.Methods We collected data from 45 patients with primary colorectal cancer without any adjuvant therapy before operation.The expression of AQP5 was measured by immunohistochemistry (IHC).Then we analyzed the correlation between AQP5 expression and clinicopathological parameters (including age,tumor size,clinical staging,tumor location,lymph node and pathological type)and the connection between AQP5 expression and prognosis based on follow-up data.Results Of the 45 tumor specimens,14 (31.1%)had a high level of AQP5 expression,29 (64.4%)exhibited a moderate level of staining,and 2 (4.4%)had an absence of AQP5 staining.AQP5 was only occasionally detected in para-neoplastic [3/45 (6.67%)]and normal tissues [3/45 (6.67%)].The overexpression of AQP5 was also positively associated with TNM stage (P =0.002),lymph node metastasis (P =0.01 6),and distant metastasis (P =0.000).However,it had no significant association with age, gender,histologic grade or tumor size (P > 0.05 ).Conclusion AQP5 may be used as a novel biomarker for predicting the prognosis of colorectal cancer.
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Objective To observe the effects ofLinggan Wuwei Jiangxin Decoction on contents of cAMP, cAMP dependent PKA and AQP5 of model rats with clod phlegm-fluid lying latent in the lung asthma;To discuss its mechanism.Methods Ovalbumin intraperitoneal injection and atomization motivation + cold stimulation were used to establish models. Ninety rats were randomly divided into blank control group, model group, hexadecadrol group, andLinggan Wuwei Jiangxin Decoction low-, medium-, high-dose groups. All administration groups were treated with relevant medicine. The levels of cAMP, PKA, and AQP5 were detected by ELISA.Results Compared with the blank control group, the levels of cAMP, PKA, and AQP5 of rats in model group decreased obviously (P<0.05). Compared with the model group, the levels of cAMP, PKA, and AQP5 of rats in all administration groups increased (P<0.05), which increased dramatically inLinggan Wuwei Jiangxin Decoction high-dose group.ConclusionLinggan Wuwei Jiangxin Decoction can regulate the normal secretion of cAMP, PKA, and AQP5 in serum of rats with clod phlegm-fluid lying latent in the lung asthma, increase secretion of air passage liquid and decrease mucoprotein concentration, through which plays the role of treating asthma.
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Purpose To investigate the expression of the protein of Ezrin and AQP5 in the normal, dysplasia gastric and carcinoma of esophagogastirc junction tissues and to find out their relationship with the biologic behavior of the carcinoma of esophagogastirc junction in the southern area of Hebei Province. Methods Ezrin and AQP5 proteins were detected by immunohistochemical staining in 10 ca-ses of normal gastric tissue, 40 cases dysplasia and 165 cases of the carcinoma of esophagogastirc junction tissues, respectively. Re-sults All of the expression levels of Ezrin and AQP5 protein were increasing according to the order of normal-dysplsia-carcinoma. The expression rate of Ezrin was 10%, 45% and 72. 7%, while the rate of AQP5 with 20%, 32. 5% and 65. 5% in the normal, dysplasia and carcinoma subgroup. The expression rates of each protein were significantly different among the three groups (P<0. 05). The ex-pression of them in the subgroup of poorly-differentiated with serosa invasion and lymph nodes metastasis was significantly higher than the other subgroup of well-differentiated with non serosa invasion or lymph nodes metastasis (P<0. 05). There was a positive correla-tion between the expression of Ezrin and AQP5 proteins in the carcinoma of esophagogastirc junction (P<0. 05). Conclusions Over-expression of Ezrin and AQP5 is detected in the carcinoma of esophagogastirc junction, with positive relationships, which probably helps the invasiveness and metastasis in the carcinoma of esophagogastirc junction synergistically.
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PURPOSE: To evaluate the effect of X-ray irradiation on apoptosis and change of expression of aquaporin 5 (AQP5) and transforming growth factor-beta(TGF-beta) in the rat submandibular gland (SMG). MATERIALS AND METHODS: SMGs of 120 male Sprague-Dawley rats were irradiated with a single X-ray dose (3, 10, 20, or 30 Gy). At the early and late post-irradiation phase, apoptosis was measured by the terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) method, and expression of AQP5 and TGF-beta was determined by immunohistochemical staining. RESULTS: At the late post-irradiation phase, increased apoptosis was evident and marked decreases of expression of AQP5 expression by acinar cells and TGF-beta expression by ductal cells were evident. CONCLUSION: Apoptosis after X-ray irradiation develops relatively late in rat SMG. Irradiation reduces AQP5 and TGF-beta expression in different SMG cell types.