Higher susceptibility of males to bleomycin-induced pulmonary inflammation is associated with sex-specific transcriptomic differences in myeloid cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA816184 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18529552_1.fastq.gz | Fastqsanger.gz | |||
| SRR18529552_2.fastq.gz | Fastqsanger.gz | |||
| SRR18529553_1.fastq.gz | Fastqsanger.gz | |||
| SRR18529553_2.fastq.gz | Fastqsanger.gz | |||
| SRR18529554_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 32 |
Similar Datasets
Project description:In this study, we subjected male and female mice to bleomycin-induced lung injury for 14-days. Bronchoalveolar lavage cells were isolated and subjected to RNA-sequencing. Four groups were compared. Saline-Males and females and bleomycin-males and females.
2022-06-10 | GSE198631 | GEO
Project description: Not available
| S-EPMC9793441 | biostudies-literature
Project description:We performed miRNA sequencing to comprehensively and unbiasedly examine the post-transcriptional landscape of lung tissue in female and male rats following bleomycin acute lung injury (ALI). Male animals displayed the greatest miRNA perturbation following lung injury with 112 miRNAs differentially expressed (75 upregulated, 37 downregulated). Female animals demonstrated markedly fewer differentially expressed miRNAs, with 66 total miRNAs (45 upregulated, 21 downregulated). Direct comparison between female and male animals’ post-injury revealed 54 differentially expressed miRNAs (8 upregulated, 46 downregulated). Baseline comparison between female and male miRNA profiles turned up 23 miRNAs (6 upregulated, 17 downregulated). Among the sex-biased miRNAs, miR-490-5p showed significant downregulation in females versus males following bleomycin-induced lung injury (log2FC = -2.40). This was particularly intriguing as miR-490-5p is predicted to target Bmpr2 (TargetScan score = 88), a critical component for vascular endothelial integrity and the BMP/TGF- signaling pathway. Correlation analysis of Bmpr2 expression and miR-490-5p expression revealed a negative correlation with females having a lower expression of miR-490-5p and a higher expression of Bmpr2 compared to males. Protein validation of BMPR2 revealed a baseline trend towards females having higher BMPR2 levels compared to males (p = 0.09), with females having significantly higher BMPR2 induction following lung injury compared to males (p = 0.009) . rno-miR-672-3p emerged as a noteworthy differentially expressed miRNA, a sex-specific regulator with opposing expression patterns between sexes. In males, miR-672-3p was significantly downregulated following bleomycin injury (log2FC = -2.46, p = 0.0003), while females showed no significant change (log2FC = 0.375, p = 0.202). Direct comparison revealed that miR-672-3p was significantly higher in bleomycin-treated females compared to bleomycin-treated males (log2FC = 2.21, p = 0.006). qPCR validation revealed a more nuanced pattern than the sequencing data suggested. Both sexes showed suppression of miR-672-3p expression following ALI compared to their respective sham controls. Male animals demonstrated the most dramatic reduction (p < 0.0001), with approximately 95% suppression relative to sham. Females also showed downregulation (approximately a 50% reduction, p = 0.0516), although the magnitude was substantially less pronounced. The direct comparison between injured males and females showed a trend toward significance (p = 0.0801), indicating high retention of miR-672-3p expression in injured females compared to males. Target prediction identified 242 potential miR-672-3p targets among male bleomycin versus sham and female versus male bleomycin DEGs, including high-confidence targeting of inflammatory mediators: Cxcr3, Cxcl11, C3ar1, Cd80, Cd4, and Serpina3a, all of which were upregulated in males in the parallel RNA-seq performed. The biological coherence of these targets, which encompass chemokine signaling, complement activation, and acute-phase responses, suggests a functional significance. To examine whether predicted miR-672-3p targets showed expression patterns consistent with mRNA expression, we analyzed correlations between miR-672-3p and target gene expression. In males, comparing injury to baseline, miR-672-3p showed negative correlations with inflammatory mediators including Cxcl11 (r = -0.88, p = 0.0008), Cxcr3 (r = -0.84, p =0.0022), Cd80 (r = -0.83, p = 0.0029), Cd4 (r = -0.78, p = 0.0083), Serpina3a (r = -0.73, p = 0.017), and C3ar1 (r = -0.77, p = 0.0086) (Figure 6D). These inverse relationships were also observed in the sex comparison with similar correlation strengths: C3ar1 (r = -0.81, p = 0.0045), Serpina3a (r = -0.80, p = 0.0054), Cd80 (r = -0.78, p = 0.0085), Cxcl11 (r = -0.78, p = 0.0148), Cxcr3 (r = -0.65, p = 0.042), and Cd4 (r = -0.77, p = 0.0089). A more granular analysis of top differentially expressed miRNAs uncovered multiple miRNAs that were upregulated in both bleomycin-treated females and males relative to their respective sham, notably miR-511-3p_R+1, though with males having higher miR-511-3p_R+1 expression relative to females following bleomycin-induced lung injury (Figure 5B. Figure S5A-D). Another miRNA mirroring a similar pattern of upregulation in both sexes post-ALI, but higher in males than females was miR-212-3p (Figure 5B). Together, these support the previous evidence of a more perturbed miRNA response in males than females. This coordinated dysregulation suggests that multiple miRNA networks beyond miR-672-3p alone contribute to sex-specific-post-transcriptional programs.
2026-04-01 | GSE324979 | GEO
Project description:A20 governs fibrosis susceptibility in bleomycin-induced mouse scleroderma model
| PRJNA800403 | ENA
Project description:Background: Preterm birth increases the long-term risk of diabetes and chronic kidney disease (CKD), yet its impact on diabetic kidney disease (DKD) is unclear. We previously showed that male preterm mice with diabetes develop early features of DKD, including reduced podocyte density, decreased renin expression, activation of angiogenesis pathways, and impaired endothelial–podocyte signaling. Here, we examine whether preterm birth similarly accelerates DKD progression in female mice and compare structural and transcriptomic outcomes in the females to the prior male cohort to assess sex-specific differences. Methods: Preterm mice were delivered by Cesarean section at 19 days post conception (dpc) and term mice at 20 dpc. Hyperglycemia was induced at 6 weeks with streptozotocin to generate term-diabetic (T-D) and preterm-diabetic (PT-D) groups; controls were term-nondiabetic (T-ND) and preterm-nondiabetic (PT-ND). Body weight and glucose were monitored, and kidneys were analyzed at 18 weeks using histologic, stereologic, imaging, and transcriptomic methods. Results: Compared with T-ND females, PT-D females showed higher albuminuria, more atubular glomeruli, reduced proximal tubule (PT) fraction, and pro-fibrotic gene activation. Compared to T-D females, PT-D females had higher blood urea nitrogen (BUN) levels and reduced PT fraction. This was associated with activation of pathways associated with the vasculature and suppression of mitochondrial metabolism gene pathways, along with Notch signaling alterations. Sex differences included a lower PT fraction in preterm females than males and fewer atubular glomeruli in PT-D females than PT-D males. Renin expression was lower in PT-D than T-D in males only. When comparing PT-D to T-D across sexes, 582 differentially expressed genes were unique to females. Notch signaling was upregulated in both male and female PT-D mice compared to T-D. Conclusion: Preterm birth increases susceptibility to kidney injury in females after exposure to hyperglycemia. However, preterm females with hyperglycemia are more resistant to kidney damage than males.
2026-05-05 | GSE319377 | GEO
Project description:We performed mRNA sequencing to comprehensively and unbiasedly examine the transcriptional landscape of lung tissue in female and male rats following bleomycin acute lung injury (ALI). Comparative analysis of bleomycin-induced ALI transcriptional responses demonstrated marked sex differences in both magnitude and directionality. Males exhibited significantly greater transcriptional perturbation with 2,393 differentially expressed genes (DEGs) (1,602 upregulated, 791 downregulated) versus 1,533 DEGs in females (1,129 upregulated, 404 downregulated) (|log2FC| ≥ 1, FDR < 0.05). Direct comparison of bleomycin-treated animals identified 826 DEGs (307 female-enriched, 519 male-enriched). Baseline sex differences were minimal, with only 262 DEGs between sham-treated animals (51 female-enriched, 211 male-enriched), indicating that observed transcriptional divergence primarily reflects sex-specific injury responses rather than constitutive sexual dimorphism. Gene Ontology (GO) analysis of these 826 DEGs began to define this polarity. The biological processes with the most divergent expression patterns included proteolysis (GO:0006508) and immune response (GO:0006955). Cellular components included both membrane and extracellular space (GO:0016020, GO:0005615), and molecular functions included protein binding (GO:0005515). KEGG pathway analysis further highlighted the contrast. Direct comparison between females and males revealed divergent pathways, including: cytokine-cytokine receptor interaction (ko04060), complement and coagulation cascades (ko04610), and ECM-receptor interaction (ko04512). A more granular analysis of the DEGs comprising these divergent functional categories and pathways identified male lungs selectively upregulating chemokines (Cxcl10, Cxcl11, Ccl17), complement/coagulation factors, (F7, Plg, C1qa), and components of the acute-phase protease inhibitor system (Timp1, Serpina3a, Tmprss9), whereas females induced BMP signaling genes (Bmpr2, Smad9, Bmp6) and an integrin scaffolding proteins (Itga1/2/9/11, Itgb3, Flrt3) . Notable findings from within-sex analyses showed females with enriched GO and KEGG themes related to extracellular matrix organization and cell-cycle progression, while males were more focused on immune pathways, specifically cytokine induction and viral response modules. A complete list of all DEGs across comparisons is provided in the supplementary materials.
2026-04-01 | GSE325299 | GEO
Project description:The uncovering of genes involved in susceptibility to the sporadic cancer types is a great challenge. It is well established that the way in which an individual deals with DNA damage is related to the chance to develop cancer. Mutagen sensitivity is a phenotype that reflects an individual’s susceptibility to the major sporadic cancer types, including colon, lung and head and neck cancer. A standard test for mutagen sensitivity is measuring the number of chromatid breaks in lymphocytes after exposure to bleomycin. The aim of the present study was to search for the pathways involved in mutagen sensitivity. Lymphoblastoid cell lines of seven individuals with a low mutagen sensitivity were compared with seven with a high score. RNA was isolated from cells exposed to bleomycin (4 hr) and unexposed cells. Micro-array analysis (19K) was used to compare gene expression of insensitive and sensitive cells. The profile of most altered genes after bleomycin exposure, analyzed in all fourteen cell lines, included genes involved in multiple processes, most prominent in cell proliferation and DNA repair. When comparing the insensitive and sensitive individuals other differentially expressed genes were found, that were involved in proliferation (e.g. BUB1) and signal transduction (e.g. DUSP4). This difference in expression profiles between mutagen sensitive and insensitive individuals justifies further studies aiming to elucidate the genes responsible for the development of sporadic cancers. Keywords: exposure to dna damaging agent, comparison of phenotypic response to dna damaging agent
2006-01-01 | GSE3598 | GEO
Project description:Bleomycin-injured alveolospheres
| PRJNA824015 | ENA
Project description:Sex differences in physiology, anatomy, behavior, and genetics are well-documented throughout the animal kingdom. These differences are often neglegted in reasearch. This imbalance can have detrimental effects, as seen in cases where certain drugs have stronger side effects in females than in males. The fruit fly, Drosophila melanogaster, presents a promising model for studying these sex-specific differences because it shares many disease-related genes and is easy to use. RNA of 10-day-old and 30-day-old D. melanogaster (w1118) was isolated and sequenced. In 10-day-old flies 3969 genes are significantly higher expressed in males than in females, and 7176 genes are significantly lower expressed in males. In 30-day-old males 3735 genes are significantly higher expressed than in females, and 7101 genes are significantly lower expressed. In detail, the present study shows that male flies exhibit higher expression levels of genes involved in toll signaling, Imd signaling, insulin signaling, and lipid metabolism. These findings highlight D. melanogaster as a valuable model organism for studying sex differences in these highly conserved signaling pathways. This model may additionally help to analyze the sex-specific effects of dietary interventions or drugs, ultimately leading to a better understanding of sex-specific interconnections and improving the development of more effective, sex-specific medical treatments.
2025-06-13 | GSE293388 | GEO
Project description:Gene expression analysis of C57BL/6 mice challenged by intratracheal bleomycin instillation: mRNA expression profiles were established from lungs following a 14-days PBS or bleomycin administration. One color -experiment with 1 strain of mice (C57BL/6) following a 14-days PBS or bleomycin administration (n=5), corresponding to a total of 10 samples.
2013-02-01 | E-GEOD-34814 | biostudies-arrayexpress