.png){kind=icon}
.png){kind=icon}
Return
HSD17B8 axis modulates Pseudomonas aeruginosa-associated lung inflammatory injury in bronchiectasis
.png){kind=icon}
OA
AI
S
C
J
K
J
J
DOI：10.1186/s13568-026-02098-2.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
Non-cystic fibrosis bronchiectasis (NCFB) is characterized by persistent Pseudomonas aeruginosa (P. aeruginosa) colonization and uncontrolled pulmonary inflammation, while the underlying metabolic regulatory mechanism remains poorly understood. This study aimed to explore the potential analyze correlations of the HSD17B8 metabolic axis in lung inflammatory injury related to P. aeruginosa in NCFB. Transcriptome sequencing was performed on peripheral blood and tissue samples from NCFB patients and healthy controls to screen differentially expressed genes. Two-sample Mendelian randomization integrated with protein quantitative trait locus data was applied to evaluate the potential association between candidate genes and NCFB susceptibility. The expression of HSD17B8 in clinical samples was further validated by RT-qPCR. Meanwhile, a rat model of P. aeruginosa-infected pulmonary inflammation was established to investigate the influences of estrone intervention on lung pathology, pro-inflammatory cytokines (IL1β, IL6), and steroid metabolite homeostasis. A total of 249 overlapping differentially expressed genes were identified. Mendelian randomization analysis indicated that downregulated HSD17B8 expression was nominally correlated with elevated NCFB risk (OR 0.76, 95% CI 0.60–0.95, P = 0.0159). Clinically, HSD17B8 was significantly decreased in NCFB patients and correlated with higher E-FACED severity scores. In the P. aeruginosa-related rat model, reduced HSD17B8 expression disturbed estradiol/estrone balance, increased IL1β and IL6 levels, and aggravated lung pathological lesions. Exogenous estrone was correlated with dose-dependent alleviation of inflammatory lesions via inhibiting inflammatory response and restoring metabolic homeostasis. Collectively, HSD17B8 is potentially involved in the progression of P. aeruginosa-associated NCFB. Altered HSD17B8 expression is associated with disturbed steroid balance and aggravated inflammatory responses related to microbial infection. Targeting HSD17B8 and its downstream steroid metabolites may offer a promising metabolic intervention strategy for P. aeruginosa-associated infectious bronchiectasis.
Keywords:
HSD17B8
Non-cystic fibrosis bronchiectasis (NCFB)
Therapeutic target
Estrone
Estradiol
Journal
IF:
3.7
Papers:
2.2K
Citations:
6.4K
Organization
Cited Papers