SRPRA affects hyperoxia-induced bronchopulmonary dysplasia by modulating endoplasmic reticulum stress through the CHOP pathway

Abstract

Background

Bronchopulmonary dysplasia (BPD) is a prevalent chronic lung disease among preterm infants, largely attributed to hyperoxia-induced injury to alveolar epithelial cells. Excessive endoplasmic reticulum (ER) stress plays a vital role in BPD progression. SRPRA, a subunit of the ER-localized SRP receptor, is upregulated in BPD, while its function and link with ER stress remain largely unclear. This study aimed to explore the role of SRPRA in hyperoxia-induced BPD and its underlying mechanism.

Methods

A hyperoxia-exposed alveolar type II epithelial cell (AECII) model was established to mimic BPD in vitro. Cell viability, cell proliferation and apoptosis were detected by CCK-8, EdU assay and flow cytometry, respectively. The secretion of inflammatory factors was evaluated via ELISA assay. ROS levels were detected by DCFH-DA fluorescence staining. Commercial kits were used to detect MDA and SOD levels. The SRPRA mRNA level and protein expression was measured using qRT-PCR and Western blot. Expression levels of apoptosis-related proteins (Bax, Bcl2), inflammation-related proteins (iNOS, Cox2) and CHOP pathway-related proteins were assessed by western blotting.

Results

SRPRA was markedly upregulated in hyperoxia-induced alveolar epithelial cells. Hyperoxia stimulation decreased viability and proliferation, and enhanced apoptosis in AECIIs, accompanied by elevated inflammatory responses and oxidative stress. SRPRA knockdown alleviated hyperoxia-induced cell damage, inflammation and oxidative stress, and downregulated the expression of CHOP (a key mediator of ER stress). The protective effects mediated by SRPRA silencing were largely reversed by thapsigargin.

Conclusion

SRPRA knockdown alleviates hyperoxia-induced AECII injury by attenuating CHOP-mediated ER stress. Our findings reveal the pathogenic role of SRPRA in BPD, and suggest SRPRA as a potential therapeutic target for this disease.

Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1186/s13019-026-04519-6.

Introduction

Bronchopulmonary dysplasia (BPD) is a major cause of morbidity and mortality related to chronic lung disease in premature infants [1]. The pathogenesis of BPD involves multiple factors, including hyperoxia-induced toxicity and inflammatory injury [2]. Prolonged hyperoxia exposure leads to excessive ROS production, induction of apoptosis in alveolar epithelial cells, inflammatory responses, and lung tissue damage, which are key pathological features of BPD [3]. Many infants with BPD continue to face significant challenges during recovery, as effective preventive or therapeutic strategies remain lacking [4]. Therefore, it is critical to investigate the pathogenesis of BPD in depth. Previous studies have identified alveolar type II epithelial cells (AECIIs) as the key target cells of BPD-associated alveolar dysplasia, which are involved in both defense mechanisms and pathological alterations following multiple stressors. Zhu et al. revealed that hyperoxia exposure triggers ferroptosis and apoptosis in neonatal AECIIs by regulating PLAGL2 and the HIF-1α/VEGF signaling pathway [5]. Moreover, Yang et al. suggested that BMSC-derived exosomes protect AECIIs from hyperoxia-induced apoptosis by activating the PI3K/AKT/mTOR signaling pathway [6]. However, the pathological mechanisms underlying AECII dysregulation in BPD progression remain to be further clarified.

ER stress is a cellular adaptive response to the accumulation of misfolded proteins in the endoplasmic reticulum lumen, which plays a key role in hyperoxia-induced lung injury [7]. AECIIs represent the primary site for the synthesis and secretion of surfactant proteins (SPs), which provide the structural and functional basis for ER stress initiation [8]. Under hyperoxia, AECIIs exhibit accumulation of misfolded or unfolded proteins, thereby activating the unfolded protein response (UPR). Under physiological conditions, the UPR acts to restore proteostasis within the endoplasmic reticulum by enhancing protein folding capacity [9]. However, under severe or prolonged stress, the ERS response shifts toward pro-apoptotic signaling. CHOP, as a major pro-apoptotic transcription factor in ER stress-related apoptosis, is significantly up-regulated during the development of ER stress [10]. It has been demonstrated that CHOP-mediated ER stress apoptosis is widely involved in a variety of organ injuries, such as type 2 diabetes mellitus [11], hepatic ischemia-reperfusion injury and myocardial infarction [12, 13]. Yang et al. found that inhibiting ER stress or CHOP expression in epithelial cells attenuates pulmonary fibrosis through Shh/HH signaling pathway [14]. However, the specific role of the CHOP-mediated ER stress apoptosis pathway in BPD pathogenesis remains unclear. Accumulating evidence has demonstrated that excessive ER stress and abnormal activation of the CHOP pathway are critical pathological drivers of hyperoxia-induced alveolar epithelial injury and BPD [15, 16]. Targeting the CHOP-mediated ER stress cascade has become a promising direction for exploring interventions against BPD.

The signal recognition particle (SRP) receptor, also known as the docking protein, is a ubiquitous and essential component of the eukaryotic co-translational protein targeting pathway. This receptor consists of two subunits, SRPRA and SRPRB, which are primarily localized to the endoplasmic reticulum (ER) membrane [17]. SRPRA plays a critical role in recognizing and binding the ribosome–nascent chain–SRP complex. Linder et al. demonstrated that loss-of-function mutations in SRP19 and SRPRA cause severe congenital neutropenia with a distinct proteome signature [18]. Child et al. further revealed the role of the SRP pathway in mRNA localization to the endoplasmic reticulum [19]. As an essential subunit of the SRP receptor complex, SRPRA is predominantly distributed on the ER membrane and participates in intracellular protein transport and ER physiological homeostasis. Given its unique localization on the ER membrane, we hypothesized that SRPRA might regulate ER stress under hyperoxic conditions. Our preliminary experiments confirmed that SRPRA expression was markedly elevated in hyperoxia-injured AECIIs. Combining the above clues, we selected SRPRA as the research object to explore its functional role in BPD and its regulatory effect on the CHOP-mediated ER stress pathway.

In the present study, we investigated whether SRPRA affects hyperoxia-induced BPD by modulating ER stress through the CHOP pathway and explored the underlying molecular mechanisms. Our study provides a new theoretical basis for the prevention and treatment of BPD.

Materials and methods

Cell culture and hyperoxia model establishment

Human alveolar type II epithelial cells (AECIIs) were purchased from Procell (CP-H209) and cultured in DMEM/F12 Complete Medium (PM150312B, Procell) supplemented with 1% penicillin-streptomycin solution (PB180120, Procell) at 37 °C with 5% CO₂. For the hyperoxia model, cells were transferred to a hyperoxia incubator containing 85% O₂/5% CO₂ for 48 h. Cells in the normoxia group were cultured for 48 h under normal conditions (21% O₂ and 5% CO₂).

Hyperoxia-induced AECII injury is accompanied by severe inflammatory responses and redox imbalance. We detected inflammatory cytokines (IL-1β, IL-6, TNF-α), inflammatory mediators (iNOS, Cox-2) and oxidative stress markers (ROS, MDA, SOD) to comprehensively evaluate the pathological status of AECIIs. Notably, AECIIs are not the primary cellular source of NO, leukotrienes or prostaglandins in lung tissue. These indicators were measured to reflect intrinsic inflammatory and oxidative damage within AECIIs under hyperoxia.

Cell transfection

Small interfering RNA targeting SRPRA (si-SRPRA) and a negative control (si-NC) were purchased from GenePharma (Shanghai, China). Cells were seeded in 6-well plates (1 × 10⁶ cells/well) and transfected with si-SRPRA or si-NC (50 nM) using Lipofectamine 3000 (Thermo Fisher Scientific) according to the manufacturer’s protocol. After 24 h of transfection, cells were exposed to hyperoxia for 6 h and/or treated with ER stress inducer thapsigargin (0.1 µM, MedChemExpress, HY-13433) for 48 h.

Cell Counting Kit-8 (CCK-8) assay

Cells were inoculated into 96-well plates (5 × 10³ cells /well) and incubated for 24 h. After 48 h of hyperoxia exposure, 10 µL of CCK-8 reagent (C6005, NCM Biotech) was added to each well and incubated at 37 °C for 2 h. Absorbance at 450 nm was measured using a microplate reader (DR-200Bs, Diatek).

EdU assay

Cell proliferation was assessed using the BeyoClick™ EdU-488 Cell Proliferation Assay Kit (C0071S, Beyotime). After 48 h of hyperoxia exposure, cells were incubated with EdU for 2 h, fixed in 4% paraformaldehyde for 30 min, and permeabilized with 0.3% Triton X-100 for 15 min. Cells were then stained with Click Reaction Butter for 30 min and Hoechst 33,342 (1:1000) for 10 min. Images were captured using a fluorescence microscope (MicroPublisher, Q-IMAGING).

Flow cytometry analysis

Cell apoptosis was detected using the Annexin V-FITC/PI Apoptosis Detection Kit (40302ES50, YEASEN). Cells were harvested, washed with PBS, and resuspended in binding buffer. Then, 5 µL of Annexin V-FITC and 10 µL of PI were added to each sample and incubated for 5 min. Apoptosis was analyzed using a flow cytometer (FACSCanto II BD Biosciences). The gating strategy was set as follows: intact cells were gated by FSC/SSC to exclude debris; then Annexin V-FITC and PI fluorescence were used to define live, early apoptotic, and late apoptotic/necrotic populations.

Enzyme-linked Immunosorbent Assay (ELISA)

IL-1β (E-EL-H0149), IL-6 (E-EL-H6156), and TNF-α (E-EL-H0109) levels in cell culture supernatants were measured using commercial ELISA kits (Elabscience, China) following the manufacturer’s protocol. The absorbance at 450 nm was assessed on a microplate reader (DR-200Bs, Diatek).

ROS detection

Cells were seeded in 96-well plates (5 × 10³ cells/well). Following 48 h of hyperoxia exposure, cells were incubated with 10 µM DCFH-DA (S0033, Beyotime) for 30 min at 37 °C. After incubation, cells were washed with PBS, and fluorescence images were acquired using a fluorescence microscope (MicroPublisher, Q-IMAGING).

Detection of MDA and SOD levels

The MDA content and SOD activity in cells were measured using the MDA Colorimetric Assay Kit (E-BC-K028-M, Elabscience) and SOD Activity Assay Kit (E-BC-K020-M, Elabscience) according to the manufacturer’s guidance. The concentrations of MDA and SOD were quantified against standard curves using a microplate reader (DR-200Bs, Diatek).

qRT-PCR analysis

Total RNA was extracted from cells with TRIzol reagent (Invitrogen, USA) in accordance with the manufacturer’s protocol. cDNA synthesis was carried out with HiScript III RT SuperMix for qPCR (R323, Vazyme). Real-time qPCR was conducted using ChamQ Universal SYBR qPCR Master Mix (Q711, Vazyme) on a CG Real Time PCR (Heal Force). Relative SRPRA mRNA expression was calculated using the 2^−ΔΔCt method. Primers are listed in Table 1.

Table 1.

Primer sequences used in this study

Gene	sense	Antisense
SRPRA	5’-TGGGTGGCTGTGCTAACAAA-3’	5’-ACAAGGCCCTTCAGCATACC-3’
GAPDH	5’-AGGTCGGAGTCAACGGATTT-3’	5’-TGACGGTGCCATGGAATTTG-3’

Western blot analysis

Total protein was extracted from ACEIIs using RIPA lysis buffer (P0013, Beyotime) and quantified using a BCA Protein Assay Kit (P0010S, Beyotime). Samples were separated by SDS-PAGE and transferred to PVDF membranes (IPVH00010, Millipore). Membranes were blocked and incubated overnight at 4 °C with following primary antibodies against: anti-CHOP (A20987, ABclonal, 1:1000; 27 kD), Cox-2 (A3560, ABclonal, 1:1000; 74 kD), iNOS (ab178945, abcam, 1:1000; 130 kD), Bax (50599-2-Ig, Proteintech, 1:2000; 21 kD), Bcl-2 (26593-1-AP, Proteintech, 1:1000; 26 kD), SRPRA (ab228625, abcam, 1:1000; 70 kD), and GAPDH (60004-1-Ig, Proteintech, 1:50000; 36 kD). After incubation with secondary antibodies (7074/7076, CST) for 2 h, protein bands were visualized using an ECL Chemiluminescent Substrate Kit (P2300, ncmbio).

Statistical analysis

Statistical analyses were performed using GraphPad Prism 8.0. All experiments were conducted in triplicate, and data are presented as mean ± standard deviation (SD). Unpaired t-tests were applied for comparisons between two groups. One-way analysis of variance (ANOVA) followed by Tukey’s post hoc test was used for comparisons among multiple groups with a single independent variable. p < 0.05 was considered statistically significant.

Results

SRPRA is highly expressed in hyperoxia-induced AECIIs

To investigate the potential role of SRPRA in BPD, we assessed the expression levels of SRPRA in AECIIs after hyperoxia exposure. As shown in Fig. 1A-C, both mRNA and protein levels of SRPRA were significantly increased in hyperoxia-treated AECIIs compared with normoxic controls. These findings suggested that SRPRA may contribute to pathogenesis of BPD.

Fig. 1.

Expression of SRPRA in the hyperoxia-treated AECIIs. (A) Relative mRNA levels of SRPRA in the hyperoxia-treated AECIIs were evaluated by qRT-PCR. (B) Determination of SRPRA level in hyperoxia-treated AECIIs through western blot assay. n = 3. Statistical analysis was performed using unpaired t-test. **P < 0.01, ***P < 0.001

SRPRA knockdown alleviated hyperoxia-induced AECII injury via ER stress

To further illustrate the effect of SRPRA on hyperoxia-induced AECII injury, we silenced SRPRA using si-SRPRA. qRT-PCR and western blot analysis were used to verify knockdown efficiency. Results in Supplementary Fig. 1 demonstrated that SRPRA knockdown markedly reduced SRPRA expression in AECIIs, confirming successful establishment of the knockdown model.

Flow cytometry showed that hyperoxia significantly increased apoptosis, which was markedly reversed by SRPRA knockdown (Fig. 2A and B). In contrast, thapsigargin abolished the anti-apoptotic effect of SRPRA silencing. Western blot analysis of apoptosis-related markers revealed that knockdown of SRPRA downregulated Bax and upregulated Bcl-2 expression in hyperoxia-exposed cells, and these effects were reversed by thapsigargin treatment (Fig. 2C-E). CCK-8 assay showed that hyperoxia reduced cell viability compared with the normal group. SRPRA knockdown restored cell viability, while thapsigargin abolished this protective effect (Fig. 2F). EdU assay showed that hyperoxia-induced inhibition of proliferation was significantly reversed by SRPRA knockdown, and this effect was partially abolished by thapsigargin co-treatment (Fig. 2G). These findings indicated that SRPRA knockdown ameliorates hyperoxia-induced AECII injury by modulating ER stress.

Fig. 2.

Effects of SRPRA knockdown on AECIIs viability, proliferation and apoptosis. AECIIs were transfected with si-NC, si-SRPRA, or si-SRPRA+thapsigargin, followed by hyperoxia treatment. (A and B) Flow cytometry assay was applied for detecting the cells apoptosis. (C-E) The protein expression of Bax and Bcl-2 was determined using western blotting. (F) AECIIs viability was determined by CCK-8 assay. (G) AECIIs proliferation was measured using EdU assay. n = 3. Statistical analysis was performed by one-way ANOVA followed by Tukey’s post hoc test. *P < 0.05, **P < 0.01, ***P < 0.001

SRPRA knockdown inhibits hyperoxia-induced inflammatory responses in AECIIs via ER stress

To investigate the role of SRPRA in hyperoxia-induced inflammation, we measured key inflammatory cytokines and enzymes using ELISA and western blotting. As presented in Fig. 3A-C, hyperoxia significantly increased the secretion of IL-1β, IL-6, and TNF-α compared with the normal group. In contrast, SRPRA knockdown markedly reduced the production of these inflammatory factors. However, the anti-inflammatory effect of SRPRA knockdown was partially attenuated by thapsigargin treatment. Furthermore, western blot analysis demonstrated that protein expression of iNOS and Cox-2 was elevated in the hyperoxia group. SRPRA silencing effectively suppressed the upregulation of iNOS and Cox-2, while thapsigargin reversed these inhibitory effects (Fig. 3D-F). Collectively, these findings suggested that SRPRA knockdown alleviates hyperoxia-induced inflammation by regulating ER stress.

Fig. 3.

Effects of SRPRA knockdown on inflammatory responses in AECIIs.The concentration of TNF-α (A), IL-1β (B), and IL-6 (C) in AECIIs was analyzed using ELISA assay. (D-F) The protein expressions of iNOS and Cox-2 were assessed using Western blot. n = 3. Statistical analysis was performed by one-way ANOVA followed by Tukey’s post hoc test. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001

SRPRA knockdown inhibits hyperoxia-induced oxidative stress in AECIIs

Next, we explored the effect of SRPRA on hyperoxia-induced oxidative stress. DCFH-DA staining showed that ROS levels were significantly higher in the hyperoxia group than in the normal group, and were significantly suppressed by SRPRA silencing. However, thapsigargin reversed the effect of SRPRA knockdown on ROS levels (Fig. 4A and B). Biochemical assays showed that MDA content was increased and SOD activity was decreased in the hyperoxia group. SRPRA knockdown reduced MDA content and enhanced SOD activity, while thapsigargin blocked these changes (Fig. 4C and D). These results suggested that SRPRA knockdown inhibits hyperoxia-induced oxidative stress in AECIIs.

Fig. 4.

Effects of SRPRA knockdown on oxidative stress in AECIIs. (A and B) DCFH-DA staining was used to detect ROS levels. (C and D) MDA content and SOD activity were elevated via commercial test kits. n = 3. Statistical analysis was performed by one-way ANOVA followed by Tukey’s post hoc test. *P < 0.05, ***P < 0.001

SRPRA modulates ER stress via the CHOP signaling pathway in BPD

To further investigate the regulatory mechanism of SRPRA in BPD, we measured the CHOP pathway-related protein expression in AECIIs. Western blot analysis revealed that SRPRA knockdown reversed the hyperoxia-induced activation of the CHOP pathway, as confirmed by reduced CHOP protein levels. However, treatment with thapsigargin cabolished the SRPRA knockdown-induced down-regulation of CHOP (Fig. 5A and B). These findings indicated that SRPRA contributes to BPD progression by regulating ER stress via the CHOP pathway.

Fig. 5.

Effects of SRPRA knockdown on CHOP pathway in AECIIs. (A and B) CHOP protein levels were detected by western blotting. n = 3. Statistical analysis was performed by one-way ANOVA followed by Tukey’s post hoc test. ***P < 0.001

Discussion

BPD is a multifactorial disorder characterized by hyperoxia-induced alveolar epithelial injury [20]. Current management relies on mechanical ventilation and pharmacotherapy, yet the lack of effective preventive or curative strategies leads to higher mortality and poorer clinical outcomes in infants with BPD compared with other preterm neonates [21] Thus, elucidating the molecular mechanisms underlying BPD pathogenesis remains critical. In this study, we demonstrate for the first time that SRPRA expression is elevated in hyperoxia-exposed AECIIs. SRPRA knockdown attenuates hyperoxia-induced cytotoxicity, restoring cell viability and proliferation while reducing apoptosis, inflammation, and oxidative stress. Mechanistically, SRPRA exerts protective effects by modulating the CHOP-dependent ER stress pathway. These findings reveal a previously unrecognized role for SRPRA in BPD pathogenesis and highlight its potential as a therapeutic target.

SRPRA, a critical component of the SRP pathway, is primarily known for facilitating protein translocation to the endoplasmic reticulum [19]. Although SRPRA expression is reportedly elevated in BPD, its functional role in disease pathogenesis remains unclear. In this study, we observed that hyperoxia significantly upregulates SRPRA expression in AECIIs, implicating it in BPD progression. Cell viability and apoptosis play pivotal roles in BPD development. For instance, Zhong et al. demonstrated that the long non-coding RNA TUG1 promotes hyperoxia-induced proliferation in MLE-12 cells while suppressing apoptosis, inflammation, and oxidative stress [22]. Zhen et al. reported that Map3k7 knockout promotes proliferation, inhibits apoptosis, inflammation, and oxidative stress in hyperoxia-induced AECIIs in BPD [23]. Consistent with these findings, our study revealed that SRPRA knockdown mitigates hyperoxia-induced lung injury by enhancing cell viability and reducing apoptosis. These results suggested that SRPRA depletion confers protection in BPD models, likely by regulating AECII homeostasis.

The inflammatory response plays a central role in BPD pathogenesis. Exposure of immature lungs to hyperoxia activates inflammatory signaling pathways, recruiting immune cells and promoting cytokine release, which induces pulmonary tissue injury and impairs alveolar development [24]. Elevated pro-inflammatory cytokine levels are strongly associated with BPD progression. For instance, Olave et al. reported that hyperoxia-induced increases in IL-6, TNF-α, and IL-1β expression in the lung tissue of mice [25]. Similarly, TNF-α, IL-6, and IL-1β concentrations significantly enhance in BPD rat model [26]. Consistent with these findings, our study demonstrated that hyperoxia promotes inflammatory response in AECIIs, characterized by increased secretion of IL-1β, IL-6, and TNF-α, along with upregulated iNOS and Cox-2 expression. Hyperoxia-induced oxidative stress is a key contributor to BPD pathogenesis. Prolonged hyperoxia disrupts redox homeostasis, leading to ROS overproduction, which activates oxidative stress-related pathways and triggers apoptosis [27]. Our data confirmed that hyperoxia elevates ROS and MDA levels and suppresses SOD activity. Notably, SRPRA knockdown attenuated these effects, underscoring its regulatory role in oxidative stress. To our knowledge, this study provides the first evidence that SRPRA is involved in hyperoxia-induced lung injury. Further research is warranted to elucidate the detailed molecular mechanisms of SRPRA in BPD.

Previous studies have demonstrated that ER stress participates in the pathogenesis of multiple diseases, including lung metastasis [28], pulmonary fibrosis [29], and lung injury [30]. Under hyperoxic conditions, ER stress activates the CHOP pathway, a critical mediator of apoptosis. Previous studies indicated that glutamine may exert therapeutic effects on BPD by improving pulmonary function through alleviating pulmonary inflammation, oxidative stress, and apoptosis [7]. Huang et al. reported that Sig-1R-regulated ER stress pathway-associated proteins (GRP78 and CHOP) in the pathogenesis of hyperoxia-induced acute lung injury [31]. This study demonstrates that hyperoxia increases CHOP expression in AECIIs. Knockdown of SRPRA downregulates these markers, indicating SRPRA inhibits CHOP-mediated ER stress. Furthermore, we used thapsigargin, an ER stress inducer that activates the CHOP pathway. Notably, thapsigargin treatment reversed the effects of SRPRA knockdown, including restoring cell viability, mitigating apoptosis, inflammation, and oxidative stress, and blocking the downregulation of CHOP pathway-associated proteins. These findings confirmed that SRPRA silencing exerts protective effects at least partially through suppressing CHOP-mediated ER stress. However, whether the regulation of CHOP by SRPRA is direct or indirect remains unclear. Further experiments such as co-immunoprecipitation (Co-IP) for protein–protein interactions and CHOP promoter luciferase reporter assays for transcriptional regulation are needed to explore the precise molecular link between SRPRA and CHOP.

Our study has several limitations. First, this study was performed using a commercial AECII cell line in vitro, which may differ from primary cells and cannot fully recapitulate the complex multicellular crosstalk and pulmonary microenvironment in vivo. Future studies are needed to validate our findings using primary AECIIs, lung organoids, or hyperoxia-exposed neonatal BPD animal models with gene manipulation techniques. Second, only SRPRA knockdown was performed, and SRPRA overexpression and rescue experiments using ER stress inhibitors were not conducted. Although our loss-of-function plus thapsigargin reversal design sufficiently supports the regulatory link between SRPRA and ER stress, further gain-of-function studies are warranted to strengthen the conclusion. Third, the direct molecular mechanism by which SRPRA regulates CHOP remains unclear, including whether it occurs via promoter binding, transcriptional regulation, or protein stability control. Further studies such as luciferase reporter assays, ChIP, and Co-IP are needed to clarify the precise interaction between SRPRA and CHOP. In addition, as a universal ER stress inducer, thapsigargin can only provide preliminary evidence for the SRPRA-ER stress regulatory relationship. The lack of validation using chemical chaperones is a shortcoming of the current design, which we will address in our future work.

Collectively, our data demonstrate that SRPRA is upregulated in hyperoxia-exposed AECIIs. Increased SRPRA activates CHOP-mediated ER stress, and further triggers cell apoptosis, inflammatory response and oxidative stress, ultimately aggravating alveolar epithelial injury. All phenotypic and molecular data jointly reveal the pathogenic role of SRPRA in BPD. Intervening SRPRA can effectively block ER stress and alleviate multiple hyperoxia-induced injuries, indicating that SRPRA is a reliable and promising therapeutic target for the prevention and treatment of BPD.

Author contributions

Yanlin Tan and Shisi Xiong contributed to Conceptualization, Data curation, Investigation, Methodology, Visualization, Project administration, Writing – original draft, and Writing – review & editing. Wenchang Ni and Liyan Wang contributed to Software, Validation, and Formal analysis. Junmei Bian contributed to Supervision, Funding acquisition, and Writing – review & editing. All authors read and approved the final manuscript.

Funding

This study was supported by the Hubei Provincial Health Commission General Project (WJ2017M186) and the Wuhan Municipal Health Commission General Projects (WX19C36, WZ21C52).

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Clinical trial

Not applicable.