Reversing multiple age-related pathologies by controlling the senescence-associated secretory phenotype of stem cells

Regenerative medicine by cell transplantation is a novel therapy for treating end-stage organ failure and tissue damage. Cell-based therapy based on the transplantation of neural stem/progenitor cells （NSPCs） represents an attractive strategy for the treatment of neurodegenerative diseases, but obtaining large numbers of these cells is difficult and their differentiation potential is strictly restricted in a spatiotemporally-regulated manner during central nervous system （CNS） development. Therefore, embryonic stem cells and induced pluripotent stem cells represent an attractive alternative for cell-transplantation therapy in regenerative medicine.

Regulation on the expression of Clara cell secretory protein in the lungs of the rats with acute lung injury by growth hormone

Background Clara cell secretory protein （CC16） is an important lung derived protective factor and may play an important role on the pathogenesis of acute lung injury （ALl） induced by endotoxemia. Growth hormone （GH） is an important anabolism hormone secreted by GH cells of the hypophysis. Previous research showed that GH would significantly exacerbate ALl induced by endotoxemia, but the mechanism is not very clear yet. Whether the effects are related to CC16 or not is undetermined. Methods One hundred and twelve male Sprague-Dawley rats were randomly divided into an ALl group and a GH group. The rats in the two groups were subdivided into seven subgroups, according to injection with lipopolysaccharides （LPS） or not, then according to different intervals of time after LPS injection; 0 hour （pre-injection of LPS, acted as control group）, 0.5 hour, 1 hour, 2 hours, 4 hours, 6 hours and 24 hours for subgroups. Pulmonary alveolar septa area density （PASAD） and ploymorphonuclear cells （PMN） in the lungs were analyzed morphometrically. The levels of tumor necrosis factor （TNF） and interleukin 6 （IL-6） were determined by radioimmunoassay. To analyze the expression and activation of nuclear factor kappa B （NF-KB）, the numbers of NF-KB positive cells in lungs were counted after immunofluorescence staining, and the levels of NF-KB inhibitory protein-a （IKB-a） in lung homogenates of rats were detected by Western blotting. The expression levels of CC16 mRNA in lungs of the rats with ALl were determined by semi-quantitative reverse transcription polymerase chain reaction （RT-PCR）. The levels of CC16 protein in lung homogenates were detected by Western blotting. Results Half an hour after LPS injury both the PASAD and PMN numbers in lungs of the rats with ALl began to increase significantly and peaked at 6-hour post-injury. They then began to recover and reached normal levels at 24-hour post-injury. Both the PASAD and PMN numbers in the GH group increased more significantly than those in the ALl group. The levels of TNF in lungs of the rats with ALl homogenates increased significantly 0.5-hour post-injury, peaked at 1-hour and maintained a high level until 6 hours then gradually recovered. The content of TNF in the GH group lung homogenates increased more significantly than in the ALl group post-injury. The contents of IL-6 in rat lung homogenates began to increase significantly at 1-hour post-injury, peaked at 4 hours then gradually returned to normal levels by 6 hours post-injury. The levels of IL-6 in the lung homogenates of the GH group were higher than in the ALl group at different time intervals post-injury. The number of NF-KB positive cells increased dramatically at 0.5-hour post-injury, and the fluorescence intensity was enhanced. Both peaked at 4-hour post-injury. The number of NF-KB positive cells and the enhanced intensity of fluorescence began to decrease from 6-hour post-injury, but the number of NF-KB cells at 24 hours post-injury was still higher than in the control group. The number of NF-KB cells in lungs in the GH group was significantly higher than in the LPS group at the different time intervals post-injury. The IKB-a expression in lungs of the rats with ALl homogenates decreased dramatically 0.5-hour post-injury, reaching a nadir at 4-hour post-injury and then began to recover. The levels of IKB-Q in GH group were significantly lower than those in ALl group. Both the levels of CC16 mRNA and protein in lungs of the rats with ALl began to decrease significantly 0.5-hour post-injury, reached a nadir at 6 hours, and then began to recover. Both the expression of CC16 mRNA and CC16 protein in the GH group were significantly lower than those in the ALl group at the different time intervals post-injury. Correlation analysis indicates that CC16 correlates significantly with all the indices mentioned above. Conclusions Down-regulation of CC16 expression plays a critical role in the pathogenesis of acute lung injury induced by endotoxemia. The application of GH can exacerbate the lung injury induced by endotoxemia through down-regulating the expression of CC16.

Functional mechanism of Pingchuanning Decoction on adjustment of clara cell secretory protein in airway remodeling of asthmatic rats

OBJECTIVE:To study the functional mechanism of Pingchuanning Decoction in treatment of airway remodeling in asthmatic rats.METHODS:Eighty healthy Wistar male rats were randomized into eight groups(n=10 rats each):Normal group,Asthma model group,Dexamethasone group,Guilong Kechuanning group,Xiaoqinglong Decoction group,and Pingchuanning Decoction low-,middle-,and high-dose groups.The rats of all but the Normal group were made into asthma models through intraperitoneal injection and aerosol inhalation of ovalbumin.All treatments were administered at the first stimulation of asthma onset(third week of modeling),and the rats were killed after stimulating asthma attacks for 4 weeks.The general conditions of rats and pathomorphological changes of the lung tissues were observed.The expression of nerve growth factor(NGF) of the lung tissues was measured with immunohistochemical methods,and the content of Clara cell secretory protein(CCSP) mRNA was determined with RT-PCR.RESULTS:Compared with the Normal group,the contents of NGF and CCSP mRNA in the lung tissues of the Model group were significantly changed(P<0.01).Compared with the Model group,the indices of Pingchuanning Decoction and other treatment groups were improved to some extent(P<0.05 or P<0.01).CONCLUSIONS:Pathological changes of airway inflammation and remodeling were present in these rat asthma models.Pingchuanning Decoction had an intervention effect on these experimental models.Its functional mechanism may be related to multiple factors,including alleviation of airway inflammation,relief of bronchial smooth muscle spasm,and inhibition of airway remodeling.