RESUMO
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with no cure except transplantation. Abnormal alveolar epithelial regeneration is a key driver of IPF development. The function of Yes1 Associated Transcriptional Regulator (YAP) in alveolar regeneration and IPF pathogenesis remains elusive. Here, we first revealed the activation of YAP in alveolar epithelium 2 cells (AEC2s) from human IPF lungs and fibrotic mouse lungs. Notably, conditional deletion of YAP in mouse AEC2s exacerbated bleomycin-induced pulmonary fibrosis. Intriguingly, we showed in both conditional knockout mice and alveolar organoids that YAP deficiency impaired AEC2 proliferation and differentiation into alveolar epithelium 1 cells (AEC1s). Mechanistically, YAP regulated expression levels of genes associated with cell cycle progression and AEC1 differentiation. Furthermore, overexpression of YAP in vitro promoted cell proliferation. These results indicate the critical role of YAP in alveolar regeneration and IPF pathogenesis. Our findings provide new insights into the regulation of alveolar regeneration and IPF pathogenesis, paving the road for developing novel treatment strategies.
RESUMO
Enhancers are a class of cis-regulatory elements in the genome that instruct the spatiotemporal transcriptional program. Last decade has witnessed an exploration of non-coding transcripts pervasively transcribed from active enhancers in diverse contexts, referred to as enhancer RNAs (eRNAs). Emerging evidence unequivocally suggests eRNAs are an important layer in transcriptional regulation. In this mini-review, we summarize the well-established regulatory models for eRNA actions and highlight the recent insights into the structure and chemical modifications of eRNAs underlying their functions. We also explore the potential roles of eRNAs in transcriptional condensates.
RESUMO
Macroautophagy/autophagy, a major catabolic pathway in eukaryotes, participates in plant sexual reproduction including the processes of male gametogenesis and the self-incompatibility response. Rapid pollen tube growth is another essential reproductive process that is metabolically highly demanding to drive the vigorous cell growth for delivery of male gametes for fertilization in angiosperms. Whether and how autophagy operates to maintain the homeostasis of pollen tubes remains unknown. Here, we provide evidence that autophagy is elevated in growing pollen tubes and critically required during pollen tube growth and male fertility in Arabidopsis. We demonstrate that SH3P2, a critical non-ATG regulator of plant autophagy, colocalizes with representative ATG proteins during autophagosome biogenesis in growing pollen tubes. Downregulation of SH3P2 expression significantly disrupts Arabidopsis pollen germination and pollen tube growth. Further analysis of organelle dynamics reveals crosstalk between autophagosomes and prevacuolar compartments following the inhibition of phosphatidylinositol 3-kinase. In addition, time-lapse imaging and tracking of ATG8e-labeled autophagosomes and depolarized mitochondria demonstrate that they interact specifically via the ATG8-family interacting motif (AIM)-docking site to mediate mitophagy. Ultrastructural identification of mitophagosomes and two additional forms of autophagosomes imply that multiple types of autophagy are likely to function simultaneously within pollen tubes. Altogether, our results suggest that autophagy is functionally crucial for mediating mitochondrial quality control and canonical cytoplasm recycling during pollen tube growth.Abbreviations: AIM: ATG8-family interacting motif; ATG8: autophagy related 8; ATG5: autophagy related 5; ATG7: autophagy related 7; BTH: acibenzolar-S-methyl; DEX: dexamethasone; DNP: 2,4-dinitrophenol; GFP: green fluorescent protein; YFP: yellow fluorescent protein; PtdIns3K: phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate; PVC: prevacuolar compartment; SH3P2: SH3 domain-containing protein 2.