RESUMEN

This paper explores the effects and influence mechanisms of environmental centralization on enterprise technological progress and productivity in China. Taking the reform of vertical environmental governance (VEG) as a quasi-natural experiment, this paper compares the differences in total factor productivity (TFP) of enterprises in environmental centralization regions and environmental decentralization regions by adopting the staggered difference-in-differences (DID) method. The empirical results show that: (1) The average TFP of enterprises in the environmental centralization areas is 0.0598 higher than that in the environmental decentralization areas, and this average effect increases with the extension of the reform duration. (2) Environmental centralization strengthens government intervention in environmental issues. The improvement in the intensity of environmental regulation and the willingness of firm green innovation are the intermediate causes of the improvement in enterprise TFP. (3) VEG's effect is heterogeneous regarding regional development, industry type, and enterprise characteristics. This study has empirical implications for further refining the fiscal system to leverage the role of public finance on environmental governance and enterprise development.

RESUMEN

Although the expression of Mex3 RNA-binding family member B (MEX3B) is upregulated in human nasal epithelial cells (HNECs) predominately in the eosinophilic chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) subtype, its functions as an RNA binding protein in airway epithelial cells remain unknown. Here, we revealed the role of MEX3B based on different subtypes of CRS and demonstrated that MEX3B decreased the TGF-ß receptor III (TGFBR3) mRNA level by binding to its 3' UTR and reducing its stability in HNECs. TGF-ßR3 was found to be a TGF-ß2-specific coreceptor in HNECs. Knocking down or overexpressing MEX3B promoted or inhibited TGF-ß2-induced phosphorylation of SMAD2 in HNECs, respectively. TGF-ßR3 and phosphorylated SMAD2 levels were downregulated in CRSwNP compared with controls and CRS without nasal polyps with a more prominent downregulation in the eosinophilic CRSwNP. TGF-ß2 promoted collagen production in HNECs. Collagen abundance decreased and edema scores increased in CRSwNP compared with control, again more prominently in the eosinophilic type. Collagen expression in eosinophilic CRSwNP was negatively correlated with MEX3B but positively correlated with TGF-ßR3. These results suggest that MEX3B inhibits tissue fibrosis in eosinophilic CRSwNP by downregulating epithelial cell TGFBR3 expression; consequently, MEX3B might be a valuable therapeutic target against eosinophilic CRSwNP.

Asunto(s)

Pólipos Nasales , Rinitis , Sinusitis , Humanos , Rinitis/complicaciones , Rinitis/metabolismo , Pólipos Nasales/genética , Pólipos Nasales/metabolismo , Factor de Crecimiento Transformador beta2/metabolismo , Sinusitis/genética , Sinusitis/metabolismo , Receptores de Factores de Crecimiento Transformadores beta/genética , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Células Epiteliales/metabolismo , Proteínas de Unión al ARN/genética

RESUMEN

BACKGROUND: The role of endoplasmic reticulum (ER) stress in the pathogenesis of allergic rhinitis (AR) remains elusive. METHODS: Real-time polymerase chain reaction (RT-PCR), immunohistochemistry, and western blotting analyses were performed to detect the expression of ER stress and unfolded protein response markers: 78-kDa glucose-regulated protein (GRP78), C/EBP homologous protein (CHOP), activating transcription factor 6 (ATF6α), spliced X-box binding protein 1 (sXBP-1), and phosphorylated eukaryotic initiation factor 2α (p-eIF2α), in inferior turbinate tissue samples from patients with AR and non-AR controls. Nasal tissues from patients with AR were cultured ex vivo and treated with 4-phenylbutyric acid (4-PBA), an ER stress inhibitor. RESULTS: Compared to those in non-AR controls, the mRNA and protein levels of GRP78, CHOP, ATF6α, sXBP-1, and p-eIF2α were significantly increased in nasal tissues from patients with AR. GRP78 and CHOP were mainly expressed in CD138+ plasma cells in nasal tissues from patients with AR. The frequency of IgE+CD138+ plasma cells was significantly higher in nasal tissues from patients with AR than that in non-AR controls. IgE levels in nasal secretions and tissues were positively correlated with GRP78 and CHOP mRNA levels in the nasal tissues. After 4-PBA treatment, the protein expression of GRP78, CHOP, ATF6α, sXBP-1, and p-eIF2α was significantly reduced in cultured AR-derived nasal tissues, and IgE levels were simultaneously decreased in cultured supernatants. CONCLUSIONS: ER stress may be involved in the regulation of local IgE production in patients with AR. Inhibition of ER stress potentially provides a therapeutic avenue in AR by reducing local IgE production. LEVEL OF EVIDENCE: NA.