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Association of Insulin-like Growth Factors with lung development in Neonatal Rats

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2004年第2期24卷 162-165页

作者：刘汉楚常立文容志惠祝华平张谦慎陈红兵李文斌 Department of Pediatrics Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

To explore the relationship between Insulin-like growth factor (IGF)- Ⅰ, -Ⅱ and lung development in neonatal rats. 80 timed pregnant Sprague-Dawley ( SD) rats were randomly divided into 4 groups (n=20): group A (Control group), group B (Dexamethasone (DEX) 1 group), group C (DEX 2 group), group D (retinoic acid (RA) group). 20 pregnant rats in group A, B and D were injected subcutaneously or intraperitoneally with vehicle (NS), DEX, or RA respectively during gestational day 16 to 18. All newborn rats in group C were subcutaneously injected with DEX at day 1 to 3 after birth. The lung tissue was obtained at the following times: fetuses at gestational ages of 18, 20 and 21 days, and 1, 3, 5, 7, 10, 14 and 21 days after birth. lung tissues were used for histopathological study, the polypeptides analysis of IGF-Ⅰ, -Ⅱ (immunohistochemistry and Western blot) and mRNA analysis ( RT- PCR). The results showed that the strongest expression of IGF-Ⅰ in group A and D occurred at ages of 5-7 days (alveolar stage). The stronger their expressions, the better the alveolar develop. The peak stage of expression in group B occurred earlier, on the day 3 after birth. Compared with group A, the expression of IGF-Ⅰ during gestation age of 18 days to age of 3 days in group B were significantly higher (Plung development in newborns. The IGF-

关键词： neonate lung development insulin-like growth factor

Effect of Retinoic acid on Platelet-derived Growth Factorand lung development in Newborn Rats

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2004年第3期24卷 226-228页

作者：陈红兵常立文刘汉楚容志惠祝华平张谦慎李文斌 Department of Pediatrics Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 China

Summary: The influence of platelet-derived growth factor (PDGF) on lung development in newborn rats and the effect of retinoic acid (RA) on PDGF in lung development were investigated. Newborn Sprague-Dawley (SD) rats were randomly assigned to two groups: control group and RA group. The rats in RA group was intraperitoneally injected with all trans-retinoic acid (500 μg/kg every day) for consecutive 3 days after birth, while those in the control group were not subjected to intervention. Immunohistochemical assay was performed to locate the expression of PDGF. mRNA levels of PDGF were measured by reverse transcription polymerase chain reaction (RT-PCR) at age of 1, 3, 5, 7, 10, 14, 21 days. The method of radial alveolar counts (RAC) was used to measure the amount of the alveoli of the lungs. It was found that with increasing days, levels of PDGF-A and PDGF-B changed to verying degrees. RA could elevate significantly the expression levels of PDGF-A mRNA and protein (P0.05). It is suggested that PDGF might play an important role in lung development. RA can stimulate lung development through increasing the expression levels of PDGF-A mRNA and protein.

关键词： platelet-derived growth factor retinoic aicd lung development newborn rats

Effects of Hyperoxia on the Dynamic Expression of Aquaporin5 in Premature Rats lung development

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2007年第3期27卷 318-320页

作者：卢红艳常立文李文斌姜娜彭琼玲蔡成刘敬 Department of Pediatrics Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

To explore the dynamic expression and role of Aquaporin5 ( AQP5) in lung development and hyperoxia lung injury, gestation 21-day Sprague-Dawley (SD) rats (term=22 days) were ran- domly assigned to air group and hyperoxia group within 12-24 h after birth. The rats in hypreoxia group were continuously exposed to about 85% oxygen and those in air group to room air. After 1 to 14 days of exposure, total lung RNA was extracted and the expression of AQP5 mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR). Immunohistochemistry and west- ern-blot were used to detect the expression of AQP5 protein. The results showed that the expression of AQP5 in premature rats lung could be detected at various time points after birth, and the positive staining was restricted to the type Ⅰ alveolar epithelial cells. In air group, the AQP5 expression was detected in a very low level at day 1, but exhibited a persistent increase after birth. Compared with the air group, the expression of AQP5 in hyperoxia group was increased at day 1, and had significant difference in mRNA level (Plung water balance. Hyperoxia exposure leads to a down-regulation of the AQP5 expression, which may be an important factor for the development of hyperoxia lung injury.

关键词： aquaporin 5 premature lung development hyperoxia water balance

Loss of Hox5 function results in myofibroblast mislocalization and distal lung matrix defects during postnatal development

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Science China(Life Sciences) 2018年第9期61卷 1030-1038页

作者： Steven M.Hrycaj Leilani Marty-Santos ANDrew J.Rasky Nicholas W.Lukacs Deneen M.Wellik Department of Internal Medicine Division of Molecular Medicine and Genetics University of Michigan Department of Pathology University of Michigan Department of Cell and developmental Biology University of Michigan

Alveologenesis is the final stage of lung development and is responsible for the formation of the principle gas exchange units called alveoli. The lung mesenchyme, in particular the alveolar myofibroblasts, are drivers of alveolar development, however,few key regulators that govern the proper distribution and behavior of these cells in the distal lung during alveologenesis have been identified. While Hox5 triple mutants(Hox5 aabbcc) exhibit neonatal lethality, four-allele, compound mutant mice(Hox5 AabbCc) are born in Mendelian ratios and are phenotypically normal at birth. However, they exhibit defects in alveologenesis characterized by a BPD-like phenotype by early postnatal stages that becomes more pronounced at adult stages. Invasive pulmonary functional analyses demonstrate significant increases in total lung volume and compliance and a decrease in elastance in Hox5 compound mutants. SMA+ myofibroblasts in the distal lung are distributed abnormally during peak stages of alveologenesis and aggregate, resulting in the formation of a disrupted elastin network. Examination of other key components of the distal lung ECM, as well as other epithelial cells and lipofibroblasts reveal no differences in distribution. Collectively, these data indicate that Hox5 genes play a critical role in alveolar development by governing the proper cellular behavior of myofibroblasts during alveologenesis.

关键词： Hox5 alveologenesis alveolar myofibroblasts lung ECM postnatal lung development

Expression of lung Surfactant Proteins SP-B and SP-C and Their Modulating Factors in Fetal lung of FGR Rats

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2015年第1期35卷 122-128页

作者：邓飞涛欧阳为相葛良芳张莉柴新群 Department of Obstetrics and Gynecology Union Hospital Tongji Medical College Huazhong University of Science and Technology

This study investigated the expression of lung surfactant proteins SP-B and SP-C, and their modulating factors TTF-1 and PLAGL2 in the fetal lung of rats with fetal growth restriction（FGR）. The rat FGR model was established by prenatal hypoxia in the first stage of pregnancy, 180 rats for experiment served as hypoxia group, and 197 healthy rats served as normal control group. The FGR incidence in hypoxia was compared with that in normal control group. The histological changes in the fetal lung were observed under the light microscope and electronic microscope in two groups. The SP-B, SP-C, TTF-1 and PLAGL2 proteins were determined in the fetal lung of two groups immunohistochemically. The expression levels of SP-B, SP-C, TTF-1 and PLAGL2 protein and m RNA in the fetal lung of two groups were detected by using Western blotting and RT-PCR respectively. The FGR rat model was successfully established by using hypoxia. Pathologically the fetal lung developed slowly, and the expression levels of SP-B, SP-C, TTF-1 and PLAGL2 protein and mR NA in the fetal lung were significantly reduced in hypoxia group as compared with those in normal control group. It was suggested that maternal hypoxia in the first stage of pregnancy could induce FGR, and reduce the expression of SP-B and SP-C, resulting in the disorder of fetal lung development and maturation.

关键词： SP-B SP-C PLAGL2 TTF-1 fetal growth restriction lung development real-time PCR Western blot immunohistochemistry

Effect of Retinoic Acid on lung Injury in Hyperoxia-Exposed Newborn Rats

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2003年第1期23卷 71-74页

作者：常立文容志惠张谦慎钱莉玲 DepartmentofPediatrics TongjiMedicalCollegeHuazhongUniversityofScienceandTechnology

To investigate whether treatment with retinoic acid (RA) could improve level of lung alveolarization and influence lung collagen in newborn rats exposed to hyperoxia, newborn Sprague-Dawley rats aged 2 days were randomly assigned to 8 groups:(1) air, (2) O 2, (3) air+NS, (4) O 2+NS, (5) air+dex, (6) O 2+dex, (7) air+RA and (8) O 2+RA. Group 2, 4 6 and 8 were kept in chambers containing 85 % oxygen, the values were checked 3 times a day. The other 4 groups were exposed to room air. Level of alveolarization and lung collagen were analyzed at age of 14 or 21 days through radial alveolar counts, alveolar airspace measurements, type Ⅰ, Ⅲ collagen immunohistochemical methods (SP method) and image processing system. Transforming growth factor-β receptors and procollagen mRNA accumulation were examined at age of 14 days through immunohistochemical methods and in situ hybridization. Our results showed that radial alveolar counts were increased and distal airspace was enlarged in group 8. TypeⅠcollagen was markedly increased, and transforming growth factor-β receptors and procollagen mRNA were decreased by retinoic acid in bronchial epithelial cells, alveolar epithelial cells and alveolar intersitium. It is concluded that retinoic acid can partially reverse lung development arrest during exposure to hyperoxia by increasing lung collagen.

关键词： retinoic acid hyperoxia lung development collagen transforming growth factor-β receptors

Comparison of protective effects of electroacupuncture and moxibustion at Zusanli(ST 36)on perinatal nicotine exposure-induced lung phenotype in rat offspring

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Journal of Traditional Chinese Medical Sciences 2023年第3期10卷 362-369页

作者： Yunpeng Ge Yitian Liu Guozhen Zhao Reiko Sakurai Yana Xie Tianyu Shi Yang Fang Jiajia Wang Virender K.Rehan Bo Ji School of Acupuncture-Moxibustion and Tuin1 Beijing University of Chinese MedicineBeijing 102488China School of Clinical Medicine Beijing University of Chinese MedicineBeijing 100029China Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center David Geffen School of Medicine at UCLALos Angeles 90502USA

Objective:To compare the effects of electroacupuncture(EA)and moxibustion at Zusanli(ST 36)on the lung phenotype of rat offspring exposed to nicotine during the perinatal ***:Pregnant Sprague-Dawley rats were randomly divided into 4 groups:the control group(saline only),the model group(nicotine only),the EA group(nicotine+EA at ST 36 acupoints bilaterally),and the moxibustion group(nicotine+moxibustion at ST 36 acupoints bilaterally).n=6 rats per *** postnatal day 21,the body weight,lung weight,and pulmonary function were determined and lung morphometry was *** proliferator-activated receptor gamma andβ-catenin levels in the lung tissue of offspring were also ***:Perinatal nicotine exposure(PNE)results in decreased body and lung weights of offspring rats,abnormal lung tissue morphology,and significantly altered pulmonary function,showing an increase in total airway resistance and a decrease in tidal volume,minute ventilation,total airway compliance,and peak expiratory *** EA at ST 36 acupoints could block all of these perinatal nicotine-induced *** moxibustion also had protective effects in nicotine-induced offspring lungs,some of these effects did not reach statistical significance,e.g.,protection against the upregulation ofβ-catenin,the downregulation of PPARγsignaling,and the increase in peak expiratory ***:Maternal EA at ST 36 blocked the PNE-induced changes in key developmental signaling pathways,prevented the PNE-induced changes in lung morphology,and protected pulmonary *** at ST 36 showed similar but weaker protective effects against the PNE-induced changes in the exposed *** is important to note that the mechanism underlying the protective effects of moxibustion at ST 36 may be different from those of EA at ST 36,and further research is needed to understand these differences.

关键词： Electroacupuncture Moxibustion Perinatal period Nicotine exposure lung development Zusanli(ST 36) PPARγ β-catenin

Regulation of Epithelial Cell Polarity during Respiratory Tubulogenesis

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Regulation of Epithelial Cell Polarity during Respiratory Tu...