Background: Alternative splicing (AS) creates different protein isoforms, an important mechanism regulating cell-specific function. Little is known about AS in lung development, particularly in alveolar type II (ATII) cells. ErbB4 receptor isoforms Jma and Jmb have significant and opposing functions in the brain, heart, and lung development and/or disease. However, the regulators of ErbB4 AS are unknown. ErbB4 AS regulators in fetal mouse ATII cells control its function in ATII cell maturation.
Methods: Candidate ErbB4 AS regulators were found using in silico analysis. Their developmental expression was studied in fetal mouse ATII cells. The effects of splice factor downregulation and upregulation on ATII cell maturation were analyzed.
Results: ErbB4-Jma increased significantly in ATII cells after gestation E16.5. In silico analysis found four candidate splice factors: FOX2, CUG/CELF1, TIAR, and HUB. Fetal ATII cells expressed these factors in distinct developmental profiles. HUB downregulation in E17.5 ATII cells increased Jma isoform levels and Sftpb gene expression and decreased Jmb. HUB overexpression decreased Jma and Sftpb.
Conclusions: ErbB4 AS is developmentally controlled by HUB in fetal ATII cells, promoting ATII differentiation. Regulated AS expression during ATII cell differentiation suggests novel therapeutic strategies to approach human disease.
Impact: Alternative splicing (AS) of the ErbB4 receptor, involving mutually exclusive exon inclusion, creates Jma and Jmb isoforms with distinct differences in receptor processing and function. The Jma isoform of ErbB4 promotes differentiation of fetal lung alveolar type II cells. The AS is mediated in part by the RNA-binding protein HUB. The molecular mechanism of AS for ErbB4 has not been previously described. The regulation of ErbB4 AS has important implications in the development of organs, such as the lung, brain, and heart, and for disease, including cancer.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9509489 | PMC |
| http://dx.doi.org/10.1038/s41390-022-02013-y | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
PLAC8 attenuates pulmonary fibrosis and inhibits apoptosis of alveolar epithelial cells via facilitating autophagy.
Commun Biol
January 2025
Department of Pulmonary and Critical Care Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
Idiopathic pulmonary fibrosis (IPF) is an irreversible lung condition that progresses over time, which ultimately results in respiratory failure and mortality. In this study, we found that PLAC8 was downregulated in the lungs of IPF patients based on GEO data, in bleomycin (BLM)-induced lungs of mice, and in primary murine alveolar epithelial type II (pmATII) cells and human lung epithelial cell A549 cells. Overexpression of PLAC8 facilitated autophagy and inhibited apoptosis of pmATII cells and A549 cells in vitro.
View Article and Find Full Text PDFLIN28A-dependent lncRNA NEAT1 aggravates sepsis-induced acute respiratory distress syndrome through destabilizing ACE2 mRNA by RNA methylation.
J Transl Med
January 2025
Emergency Department, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630, China.
Background: Acute respiratory distress syndrome (ARDS) is a life-threatening and heterogeneous disorder leading to lung injury. To date, effective therapies for ARDS remain limited. Sepsis is a frequent inducer of ARDS.
View Article and Find Full Text PDFActivated DRP1 promotes mitochondrial fission and induces glycolysis in ATII cells under hyperoxia.
Respir Res
December 2024
Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
Backgroud: Recent studies have reported mitochondrial damage and metabolic dysregulation in BPD, but the changes in mitochondrial dynamics and glucose metabolic reprogramming in ATII cells and their regulatory relationship have not been reported.
Methods: Neonatal rats in this study were divided into model (FIO2:85%) and control (FIO2: 21%) groups. Lung tissues were extracted at 3, 7, 10 and 14 postnatal days and then conducted HE staining for histopathological observation.
Mechanism of miR-130b-3p in relieving airway inflammation in asthma through HMGB1-TLR4-DRP1 axis.
Cell Mol Life Sci
December 2024
Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji, 133002, People's Republic of China.
Asthma is a chronic inflammatory respiratory disease characterized by recurrent breathing difficulties caused by airway obstruction and hypersensitivity. Although there is diversity in their specific mechanisms, microRNAs (miRNAs) have a significant impact on the development of asthma. Currently, the contribution of miR-130b-3p to asthma remains elusive.
View Article and Find Full Text PDFFetal Tracheal Occlusion Corelates with Normalized YAP Expression and Alveolar Epithelial Differentiation in CDH.
Am J Respir Cell Mol Biol
December 2024
Massachusetts General Hospital, Pediatrics, Boston, Massachusetts, United States;
Congenital diaphragmatic hernia (CDH) is characterized by incomplete closure of the diaphragm. While the ensuing compression to the fetal lung causes lung hypoplasia, specific cellular phenotypes and developmental signaling defects in the alveolar epithelium in CDH are not fully understood. Employing lung samples from human CDH, a surgical lamb model and a nitrogen rat model, we investigate whether lung compression impairs alveolar epithelial differentiation and Yes-associated protein (YAP)-mediated mechanosensing.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!