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Many circular RNAs(circRNAs)have been discovered and identified as noncoding RNA in various organisms in a specie-, tissue-, disease-and developmental stage-specific manner, and have been demonstrated to play essential roles in myriad life processes, such as embryo and tissue development, aging, insulin secretion, vascular disease and cancer.The normal development of lung morphology, structure and function is the physiological basis of breath.Accumulating evidences have been demonstrated that circRNAs might be involved in lung development and play important roles in lung development and related diseases like bronchopulmonary dysplasia(BPD).This review will summarize the biological functions of circRNAs and focus particularly on the potential implications of circRNAs in lung development and BPD.
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As a member of vessel extracellular matrix, pericytes have a close relationship with angiogenesis.Pericytes widely exist on the surface of microvascular all over the body, which are important to the stability of vessels.As a member in development of vascular structure, pericytes are located in the niches between the junction of lung vascular cells, and pericytes definitely play important roles in lung development and lung diseases.Based on the functional characters of pericytes, this article summarizes the relevant researches about the roles of pericytes in the lung development and lung diseases, and further study of pericytes will provide new insights into the mechanism of lung development and lung diseases.
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Bronchopulmonary dysplasia (BPD) is a common respiratory disease in preterm infants.Infection, inflammation and oxidative stress are the main pathogenic mechanisms of BPD.Recent studies have shown that the colonization of pulmonary microorganisms begins from the perinatal period and dynamically changed by multiple factors.Respiratory microecology dysbiosis may trigger oxidative stress, inhibit the expression of miR-876-3p, change pulmonary metabolism and weaken local barrier function, thereby leading to the occurrence and progress of BPD.At the same time, abnormal pulmonary development and lung injury also exert impact on respiratory microecology, and the impact even lasts till adulthood.Probiotics have anti-inflammatory, anti-infection and antioxidant effects.Supplementation of probiotics may promote lung development and alleviate lung injury conditions by regulating respiratory microecology.In this article, the establishment and dynamic changes of neonatal respiratory microecology were elaborated, and the role of respiratory microecology in the pathogenesis, prevention and treatment of BPD was explored.
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Objective:To investigate the effects of 4-hydroxy-2, 2, 6, 6-tetramethylpiperidine (Tempol) on the expressions of hypoxia inducible factor-1 α (HIF-1α)/vascular endothelial growth factor (VEGF) and lung development in premature neonatal rats under intermittent hypoxia (achieved by supplying a low concentration of oxygen).Methods:The intermittent hypoxia model was established.Caesarean section of rats was performed at 21 days of gestation when the fetal rats were estimated to be in labor.A total of 192 premature neonatal rats survived and were randomly divided into 6 groups according to random number table method: air control+ saline group, air control+ Tempol group, constant oxygen + saline group, constant oxygen + Tempol group, intermittent hypoxia + saline group, and intermittent hypoxia + Tempol group, 32 rats in each group.On the 7 th, 14 th and 21 st day of birth, the lung tissues of 8 neonatal preterm rats in each group were taken.Malondialdehyde (MDA) and total antioxidant capacity (TAOC) were detected by chemical analysis.The mRNA and protein levels of HIF-1α and VEGF were detected by real-time fluorescence quantitative PCR (qPCR) and immunohistochemistry, respectively.Another 8 neonatal rats in each group were taken for pulmonary function test on the 21 st day after birth. One- way ANOVA and SNK- q test were used for comparison among and between groups, respectively. Results:Compared with the constant oxygen + saline group, the intermittent hypoxia + saline group showed mild pulmonary septal thickening, increased MDA, decreased TAOC, elevated mRNA and protein expression levels of VEGF and HIF-1 α, and decreased lung function indexes.The differences were statistically significant (all P<0.05). Compared with the corresponding saline group, the intermittent hypoxia + Tempol group had decreased MDA and increased TAOC, and the differences were statistically significant at 14 d[MDA(3.09±0.45) nmol/(mg·pr) vs.4.02±0.30) nmol/(mg·pr), TAOC(3.13±0.31) U/(mg·pr) vs.(2.44±0.22) U/(mg·pr)]and 21 d[MDA(2.87±0.43) nmol/(mg·pr) vs.(4.47±0.56) nmol/(mg·pr), TAOC(3.47±0.35) U/(mg·pr) vs.(2.31±0.32) U/(mg·pr)] (all P<0.05). Compared with the corresponding saline group, the mRNA and protein expression of HIF-1 α and VEGF decreased in the intermittent hypoxia+ Tempol group, and the decrease in the mRNA expression of HIF-1 α was statistically significant at 14 d (2.11±0.60 vs.2.88±0.59) (all P<0.05). Lung function indexes, including tidal volume[(0.41 ± 0.01) mL vs.(0.36±0.02) mL], minute respiratory ventilation[(35.48 ± 2.95) mL vs.(30.62±2.27) mL], maximum expiratory flow[(2.19 ± 0.19) mL/s vs.(1.51±0.19) mL/s]and dynamic lung compliance[(2.65 ± 0.40) mL/cmH 2O vs.(1.83±0.34) mL/cmH 2O, 1 cmH 2O=0.098 kPa]increased (all P<0.05). Conclusions:Tempol can alleviate the lung injury induced by intermittent hypoxia under the intervention of a low concentration of oxygen to premature newborn rats and improve their lung function.
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OBJECTIVE@#To investigate the protective effect of electroacupuncture (EA) at "Zusanli" (ST 36) in pregnant rats on lung dysplasia of newborn rats with intrauterine growth restriction (IUGR) induced by maternal food restriction.@*METHODS@#Twenty-four female SD rats were randomly divided into a control group, a control+EA group, a model group and a model+EA group, 6 rats in each group. From the 10th day into pregnancy to the time of delivery, the rats in the model group and the model+EA group were given with 50% dietary restriction to prepare IUGR model. From the 10th day into pregnancy to the time of delivery, the rats in the control+EA group and the model+EA group were treated with EA at bilateral "Zusanli" (ST 36), once a day. The body weight of offspring rats was measured at birth, and the body weight and lung weight of offspring rats were measured on the 21st day after birth. The lung function was measured by small animal lung function detection system; the lung tissue morphology was observed by HE staining; the content of peroxisome proliferator activated receptor γ (PPARγ) in lung tissue was detected by ELISA.@*RESULTS@#Compared with the control group, the body weight at birth as well as the body weight, lung weight, lung dynamic compliance (Cdyn) and PPARγ at 21 days after birth in the model group were significantly decreased (@*CONCLUSION@#EA at "Zusanli" (ST 36) may protect the lung function and lung histomorphology changes by regulating the level of PPARγ of lung in IUGR rats induced by maternal food restriction.
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Animals , Female , Pregnancy , Rats , Acupuncture Points , Electroacupuncture , Fetal Growth Retardation/therapy , Lung , Rats, Sprague-DawleyABSTRACT
Lung development in premature infants includes alveolar cell differentiation,pulmonary vascular development,alveolar maturation.Vitamin D plays an important role in lung development in premature infants.Studies suggest that premature infants are often deficient or insufficiency in vitamin D.Low vitamin D levels,vitamin D binding protein polymorphisms,and vitamin D receptor gene polymorphisms increase the incidence of bronchopulmonary dysplasia and neonatal respiratory distress syndrome.Vitamin D regulates lung development in premature infants by promoting pulmonary vascular development,reducing inflammatory damage to alveolar epithelial cells,and promoting alveolar maturation,thereby reducing the risk of bronchopulmonary dysplasia,neonatal respiratory distress syndrome,and persistent pulmonary hypertension of newborn.This article reviews the relationship between vitamin D and lung development in premature infants.
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Bronchopulmonary dysplasia(BPD)is the most common chronic respiratory disease in premature and low birth weight infants, characterized by alveolar and pulmonary vascular dysplasia.This article reviews the factors related to the pathogenesis of BPD, with the aim of providing new ideas for the research of pathogenesis of BPD and its prevention and treatment.Among them, immature lung development, acute lung injury, and abnormal repair after injury are the key links of BPD.Other influencing factors include oxygen poisoning, barotrauma, infection, lack of nutritional support, patent ductus arteriosus, blood transfusion, gastroesophageal reflux, pulmonary interstitial edema, abnormal coagulation function, cholestasis and so on.
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Objective To investigate the effects of different concentration hyperoxic exposure on the lung development of neonatal rats for providing theoretical basis for the preparation of bronchopulmonary dys-plasia model. Methods A total of 128 newborn rats were randomly and equally assigned to one of the fol-lowing four groups:group A(FiO2 >0. 9,n＝32),group B ( FiO2 ＝0. 6,n＝32),group C(FiO2 ＝0. 4,n＝32) and the air group(21% O2,n＝32). Lung tissue were collected at day 3,7,14 and 21 for histological analysis. Body weights were recorded,pulmonary morphology and radical alveoli count(RAC),mean alveolar diameter(MAD),alveolar septal thickness(AST) were carried out. Results Compared with the air group of the same time,the body weight of group A significantly decreased at 3 d( P <0. 05),the body weight of group B significantly decreased at 7 d(P<0. 05),the body weight of group C slightly decreased at every time point,but there was no statistical significance(P>0. 05). HE staining showed that the alveolar cavity signifi-cantly increased,alveolar structure was simplified and the alveolar spacing was thickened in different degrees in group A and group B. Furthermore,the reduction in the number of alveoli was more obvious and the alveo-lar septum was thicker in group A. The change of alveoli in group C was obviously weaker than group A and group B. The RAC of group A and group B were significantly lower than those in the air group(P<0. 05). The RAC of group C was slightly lower than those in the air group,and had statistical significance at 14 d (P<0. 05). The MAD and AST of group A and group B were significantly higher than those in the air group at 7 d (P<0. 05). The MAD and AST of group C decreased slightly over time,and had statistical signifi-cance at 21 d( P<0. 05). Conclusion Different concentrations of oxygen can have an impact on alveolar development. Severe alveolar dysplasia can be seen after continuous inhalation of more than 60% oxygen concentration. It provides a model basis for the study of the pathogenesis of bronchopulmonary dysplasia.
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GATA transcription factors encode a zinc finger DNA binding protein and play an important role in regulating cell proliferation and differentiation.GATA6 is an important member of the GATA transcription factor family,mainly expressed in the tissues and organs derived from endoderm.It is also the most fundamental member of the GATA family located in the airway epithelial cells.It is involved not only in the regulation of normal lung tissue development,but also in the pathogenesis of lung diseases.This review focuses on the role of GATA6 in lung development and some lung diseases.
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Objective To investigate the role of CCAAT enhancer binding protein A (C/EBPα) in lung development by analyzing the relationship between dynamic expression of C/EBPα protein and cell differentiation in rat lung tissue.Methods According to the histological stages of rat lung development,lung tissues were collected on 15.5 d (the late pseudoglandular period),17.5 d (the canalicular period),19.5 d (the early saccular period) of embryonic age and at 12 h (the middle saccular period),on 4 d (the late saccular period),7 d (the alveolar period,the alveolar stage),14 d (the alveolar period,the equilibrium stage) of postnatal age.The lung morphologic appearance was observed by using HE staining.Western blot was used to detect the expressions of C/EBPα and surfactant Protein (SP)-A,SP-B,SP-C,SP-D.Phosphatidylcholine (PC) assay kit was utilized to analyze the secretion of PC.Periodic acid-schiff (PAS) staining was used to evaluate the amcunt of glycogen in lung tissue.Results (1) C/EBPαt and SP-A began to express on 15.5 d of embryonic age (0.36 ±0.02,0.01 ±0.01),while SP-B,SP-C and SP-D started to express on 17.5 d of embryonic age (0.33 ±0.06,0.01 ±0.01,0.11 ±0.08).All of them increased with the development of lung,and C/EBPα,SP-A,SP-C reached the highest level at 12 h of postnatal age (3.48 ±0.05,3.24 ± 0.19,1.26 ± 0.21),and SP-D on the postnatal 4 d (1.48 ± 0.10),then gradually decreased,while the expression of SP-B continued to rise.The levels of C/EBPα and SPs maintained stable on postnatal 14 d.The C/EBPα protein level was positively correlated with SPs at embryonic age of 15.5 d,17.5 d,19.5 d and postnatal age 12 h (r =0.999,0.991,0.982,0.951,all P ＜ 0.05).(2) The level of PC was very low at embryonic age of day 15.5 [(60.50 ± 1.30) μg/g].With the development of lung,the secretion of PC increased gradually,but there was no significant correlation between the expression of PC and C/EBPoα(all P ＞ 0.05).(3) The level of glycogen was high in the late pseudoglandular stage (15.5 d) (585.50 ± 2.20),the content of glycogen decreased with the development of lung,especially on the canalicular (embryonic day 17.5) and during early saccular period (embryonic day 19.5),and then it became stable during the alveolar period (postnatal age 7 d).The expression of C/EBPα had negative correlation with the content of glycogen in fetal lung(r =-1.000,P ＜ 0.01).Conclusion C/EBPα plays an important role in rat lung development,as it may promote lung maturation by regulating the synthesis and secretionof SPs and PC.
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Bronchopulmonary dysplasia (BPD) is the most common chronic respiratory disease in premature and low birth weight infants,characterized by alveolar and pulmonary vascular dysplasia.This article reviews the factors related to the pathogenesis of BPD,with the aim of providing new ideas for the research of pathogenesis of BPD and its prevention and treatment.Among them,immature lung development,acute lung injury,and abnormal repair after injury are the key links of BPD.Other influencing factors include oxygen poisoning,barotrauma,infection,lack of nutritional support,patent ductus arteriosus,blood transfusion,gastroesophageal reflux,pulmonary interstitial edema,abnormal coagulation function,cholestasis and so on.
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OBJECTIVE@#To compare the effects of electroacupuncture (EA) at "Zusanli" (ST 36) versus "Yanglingquan" (GB 34) in the pregnant rats on perinatal nicotineexposureinduced lung function and morphology of newborn rats and explore the rule of acupoint effect in EA for the prevention from lung dysplasia in newborn rats.@*METHODS@#A total of 24 female SD rats were randomized into a normal saline group (S group), a nicotine group (N group), a nicotineST 36 group (N + ST 36 group) and a nicotineGB 34 group (N+GB 34 group), 6 rats in each one. Starting at the 6th day of pregnancy, 0.9% sodium chloride solution was injected subcutaneously in the S group, 1 mg/kg; and in the rest 3 groups, nicotine of the same dose was injected through to the 21st postnatal day to establish the perinatal nicotineexposure model. Simultaneously, during model preparation, EA was applied at "Zusanli" (ST 36) and "Yanglingquan" (GB 34) in the N+ST 36 group and the N+GB 34 group respectively, once a day, through to the 21st postnatal day. The lung function analytic system for small animal was adopted to observe the changes in lung function indicators in newborn rats, such as peak inspiratory flow (PIF), peak expiratory flow (PEF), expiratory resistance (RE), inspiratory resistance (RI) and dynamic compliance (Cdyn). HE staining was used to observe the morphological changes of lung, such as alveolar fusion and rupture.@*RESULTS@#Compared with the S group, PEF and Cdyn were lower and PIF, RI and RE higher in the N group (all 0.05).@*CONCLUSION@#Electroacupuncture at "Zusanli" (ST 36) in the pregnant rats significantly improves the perinatal nicotineexposureinduced lung function and morphology of newborn rats than electroacupuncture at "Yanglingquan" (GB 34).
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Animals , Female , Pregnancy , Rats , Acupuncture Points , Animals, Newborn , Electroacupuncture , Lung , Nicotine , Toxicity , Random Allocation , Rats, Sprague-DawleyABSTRACT
Long non-coding RNA (lncRNA) defined as ncRNAs of more than 200 nt in length.LncRNA is widely distributed and is involved in a variety of physiological and pathological processes of lung.In addition,lncRNA plays an important role in regulating the initiation and development of lung cancer.More details about mechanisms of lncRNA regulation of lung physiology and pathology are not clear.This review summarizes the mechanisms and current status of lncRNA associated with lung development and lung diseases,which provides insights in the relationship between lncRNA and respiratory system.
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SOX4 is a member of the group C subfamily of the SOX transcription factors and has a criti-cal role during embryogenesis and in controlling cell fate.SOX4 can participate in TGF-β,Wnt signaling ways to mediate cell differentiation,proliferation,migration.SOX4 can facilitate epithelial-mesenchymal transition by di-rectly regulating EZH2 expression.It is one of the 64 genes that constitute a general signature in all human canc-ers.SOX4 is widely expressed in lung and establishes the lung structure in lung development.Here,we provide an overview of role of SOX4 in cell and lung development.
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Pulmonary diseases are seriously harmful to the health of the newborns and children.Understanding the pathogenesis of pulmonary diseases,carrying out effective prevention and accurate diagnosis are challenges for pediatrician.Previous study demonstrated that lung development defects are source of disease susceptibility and closely associated with newbom's and children(s) pulmonary diseases.This article will focus on lung development,introducing the impact factor and the key regulatory molecules about lung development and pulmonary development defect related diseases which will provide important insights for clinician to explore the mechanism of pulmonary diseases.
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Objective To explore the effects of prenatal infection on the development of lungs by dynamic observation of morphology and numbers of inflammatory cells in lungs of rat pups exposed to antenatal inflammation.Methods Pregnant Wistar rats were randomly divided into experimental group and control group.Pregnant rats of both groups were intraperitoneal injected with either lipopolysaccharide (LPS) 2.5mg/kg or the same volume of normal saline on embryonic day 19 and 20, respectively, and were allowed to term deliver.Onday1, 3, 7, 14, 21and28 (D1, D3, D7, D14, D21 andD28), eight pups of each group were killed by 10％ chloral hydrate (1ml/kg) and lungs were collected.The numbers of myeloperoxidase (MPO) and CD68 as markers of both neutrophils and macrophages were counted.Morphometric assessments were performed by measuring the mean numbers of alveolar, the mean ratio of alveolar surface area to per tissue and the mean thickness of alveolar septum.Results With the increasing of postnatal days, the mean numbers of alveolar and the mean ratio of alveolar surface area to per tissue in both groups increased.The mean thickness of alveolar septum got thinner and the numbers of inflammatory cells decreased.On D1, D3, D7 and D14, the mean alveolar numbers of the experimental group (88, 89, 102 and 127 /mm2) were significantly less than those of the control group (105, 109, 123, 156/mm2), P =0.024, 0.009, 0.013, 0.004, respectively.On D1, D3 and D7, the mean ratios of alveolar surface area to per tissue were significantly larger (0.552,0.603 and0.533) than those of control group (0.478, 0.485 and 0.404), P=0.003, 0.001, 0.000, respectively.On D1 and D3, the alveolar septum thickness was significantly thinner (12.30 and 10.75 μm) thanthatin control group (17.13 and 16.13 μm), P=0.000, 0.000, respectively.On D1, D3, D7 and D14, the mean numbers of neutrophils of the experimental group (681, 582, 393 and 379/mm2) were significantly more than those of control group (164, 211, 145 and 179 /mm2), P =0.000, 0.000, 0.000,0.003, respectively.On D1, D3 and D7, the mean numbers of macrophages (613, 578 and 337 /mm2)were significantly more than those of control group (170, 182 and 127, /mm2) , P=0.000, 0.000, 0.000,respectively.Conclusion Prenatal infection results in larger and fewer alveolars and more inflammatory cells in lungs of rat pups.With the increasing of postnatal days, the alveolar morphology was similar to the controis.
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MicroRNAs are composed of a large group of small, non-coding RNA sequences that are highly conserved among species.So far, researchers have uncovered that microRNAs play important roles in various biological processes including developmental timing, cell fate determination, immune responses, insulin secretion, and progression of various cancers.Recently, microRNAs have become a major focus of interest for research in lung development.This article provides an overview of the various microRNAs that have been implicated in lung organogenesis.
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Recent studies show that vitamin D plays a role in lung development and regulation of lung maturation in the fetus. The AAP and the Institute of Medicine( IOM) both define vitamin D insufficiency as ser-um 25-OH-D concentrations <50 nmol/L in the pediatric population. The surveys in our country show the prev-alence of vitamin D insufficiency is higher according to the criteria defined by AAP. Evidence from animal study suggests that vitamin D may increase alveolar count,alveolar septal thickness,lung volume and decrease airway resistance,immune cell aggregation leading to the maturation of lung. The cohort studies suggest low 25-OH-D level in infants at birth is associated with greater need for assisted ventilation,increased rate of ARDS,increased duration of oxygen requirement.
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mTOR signaling pathway is a highly conserved intracellular signaling pathway,which partici-pates in several signaling pathways, such as PI3K/AKT/mTOR, AKT/TSC1-TSC2/Rheb/mTOR, LKB1-AMPK-TSC-mTOR and FGF-10-Spry2-mTORC1-STAT3/HIF-1α-VEGF-A. mTOR signaling implicate in the regulation of the development of lung and many pulmonary diseases in many aspects,may be connected to bron-chopulmonary dysplasia. Bronchopulmonary dysplasia is one of the very common chronic lung diseases in pre-term,physical and chemical factors have been shown to induce acute lung injury, aberrant wound healing and lung fibrosis in the immature lung. This review summarizes relationship of mTOR signaling among lung develop-ment,acute lung injury and lung fibrosis,to explore the role of mTOR signaling in the development of bronchop-ulmonary dysplasia,in hope of providing novel method in the prevention and treatment of bronchopulmonary dysplasia.
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miRNAs are a group of 22 ~25 nucleotides endogenous non-coding RNAs,which regulate gene expression at the post-transcription level by cause the degradation or translational suppression of target mR-NAs.In recent years,studies have demonstrated that miRNAs widely participate in cell differentiation,prolifera-tion,organ development and lipid metabolism,and are closely related to the formation of many kinds of diseases. The biological function of miRNAs and their effects on regulating prenatal and postnatal lung development are reviewed in this paper.