3aired Capacity of Fibroblasts to Support Airway Epithelial Progenitors in Bronchiolitis Obliterans Syndrome

Background： Bronchiolitis obliterans syndrome （BOS） often develops in transplant patients and results in injury to the respiratory and terminal airway epithelium. Owing to its rising incidence, the pathogenesis of BOS is currently an area of intensive research. Studies have shown that injury to the respiratory epithelium results in dysregulation of epithelial repair. Airway epithelial regeneration is supported by stromal cells, including fibroblasts. This study aimed to investigate whether the supportive role of lung fibroblasts is altered in BOS. Methods： Suspensions of lung cells were prepared by enzyme digestion. Lung progenitor cells （LPCs） were separated by fluorescence-activated cell sorting. Lung fibroblasts from patients with BOS or healthy controls were mixed with sorted mouse LPCs to compare the colony-forming efficiency of LPCs by counting the number of colonies with a diameter of_〉50/.tln in each culture. Statistical analyses were pertbrmed using the SPSS 17.0 software （SPSS Inc., USA）. The paired Student＇s t-test was used to test tbr statistical significance. Results： LPCs were isolated with the surface phenotype ofCD31-CD34-CD45- EpCAMtSca- I . The colony-lbrming efficiency of LPCs was significantly reduced when co-cultured with fibroblasts isolated from patients with BOS. The addition ofSB431542 increased the colony-forming efficiency of LPCs to 1.8%; however, it was still significantly less than that in co-culture with healthy control fibroblasts （P 〈 0.05）. Conclusion： The epithelial-supportive capacity offibroblasts is impaired in the development of BOS and suggest that inefficient repair of airway epithelium could contribute to persistent airway inflammation in BOS.

Hepatic Cyp1a2 Expression Reduction during Inflammation Elicited in a Rat Model of Intermittent Hypoxia

Background： Intermittent hypoxia （IH） is a key element of obstructive sleep apnea （OSA） that can lead to disorders in the liver. In this study, IH was established in a rat model to examine its effects on the expression of hepatic cytochrome P450 （CYP） and CYP regulators, including nuclear receptors. Methods： Hematoxylin and eosin staining was conducted to analyze the general pathology of the liver of rats exposed to IH. The messenger RNA （mRNA） expression levels of inflammatory cytokines, CYPs, nuclear factor-κB （NF-κB）, and nuclear factors in the liver were measured by quantitative reverse transcription polymerase chain reaction. Results： We found inflammatory infiltrates in the liver of rats exposed to IH. The mRNA expression level of interleukin-1beta was increased in the liver of the IH-exposed rats （0.005 ± 0.001 vs. 0.038 ± 0.008, P = 0.042）, whereas the mRNA expression level of Cyp1a2 was downregulated （0.022 ± 0.002 vs. 0.0050 ± 0.0002, P = 0.029）. The hepatic level of transcription factor NF-κB was also reduced in the IH group relative to that in the control group, but the difference was not statistically significant and was parallel to the expression of the pregnane X receptor and constitutive androstane receptor. However, the decreased expression of the glucocorticoid receptor upon IH treatment was statistically significant （0.056 ± 0.012 vs. 0.032 ± 0.005, P = 0.035）. Conclusions： These results indicate a decrease in expression of hepatic CYPs and their regulator GR in rats exposed to IH. Therefore, this should be noted for patients on medication, especially those on drugs metabolized via the hepatic system, and close attention should be paid to the liver function of patients with OSA-associated IH.

Sex-determining region Y-box 2-positive alveolar cells are responsive to bleomycin-induced lung injury

As an important barrier,the pulmonary alveolar epithelium plays an important role in lung gas exchange and host defense.The alveolar epithelium is mainly comprised of alveolar type I(AT1)and type II(AT2)cells that are tightly connected to maintain the integrity of the alveolar epithelium.There are several kinds of stem/progenitor cells capable of repairing the adult alveolar epithelium in response to various injuries.Kim and colleagues identified bronchioalveolar stem cells(BASCs)that are capable of differentiating into alveolar cells and airway cells.[1]In addition,a subset of alveolar cells expressing the laminin receptorα6β4 but not surfactant protein C(SPC)was able to regenerate into AT2 cells upon bleomycin-induced lung injury.[2]Rare keratin 5-positive basal cells give rise to alveolar epithelial lineages after influenza infection.[3,4]Sex-determining region Y-box 2(Sox2)is a transcription factor that maintains and regulates self-renewal and pluripotency in embryonic stem cells.[5]The functional roles of Sox2 in the repair of alveolar epithelium injuries remain unknown.This study aimed to investigate whether the alveolar cells expressing Sox2 are involved in alveolar epithelial repair.

Unlocking lung regeneration:insights into progenitor cell dynamics and metabolic control

Regenerative responses are particularly important in the lungs,which are critical for gas exchange and frequently challenged by environmental insults.The lung progenitor cells play a central role in the lung regeneration response,and their dysfunction is associated with various lung diseases.Understanding the mechanisms regulating lung progenitor cell function is essential for developing new therapeutic approaches to promote lung regeneration.This review summarizes recent advancements in the field of lung regeneration,focusing on the metabolic control of lung progenitor cell function.We discuss cell lineage plasticity and cell–cell signaling under different physiological condi-tions.Additionally,we highlight the connection between progenitor cell dysfunction and lung diseases,emphasizing the need to develop new therapeutic strategies in regenerative medicine to improve lung regenerative capacity.