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Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

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Integrative multi-omics profiling implicates purine metabolism and the PI3K-Akt pathway in radiation-induced lung

Jun Qiu¹, Xinpan Li², Yi Fang³

¹Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region 530021, PR China; Department of Oncology, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan 410006, PR China; Department of Oncology, Changsha County People's Hospital (Hunan Provincial People's Hospital Xingsha Campus), Changsha 410000, China.

|January 25, 2026

Abstract

Background:

Thoracic radiotherapy commonly causes radiation-induced lung injury (RILI); however, its mechanisms remain poorly defined, and no FDA-approved therapies are available.

Methods:

To identify key pathways and regulators, we analyzed metabolic and transcriptomic alterations in a murine model of RILI. Following a 15 Gy thoracic irradiation, lung tissues were assessed by histopathology (H&E and Masson staining), LC-MS-based metabolomics, and transcriptomics.

Results:

Irradiated lungs showed erythrocyte exudation, inflammatory infiltration, fibrosis, and epithelial damage, whereas control tissues showed no pathological changes. Metabolomic profiling identified 186 differentially abundant metabolites, primarily enriched in purine and glycine/serine/threonine metabolism. Transcriptomics revealed 180 differentially expressed genes. Integrative analysis demonstrated that both metabolites and genes converged on the PI3K-Akt and phospholipase D signaling pathways, suggesting their potential as early RILI biomarkers. Analyses also revealed a consistent association between RILI and lung microbiota dysbiosis, pointing to novel mechanistic insights.

Conclusions:

Our integrative multi-omics analysis reveals that RILI progression is characterized by dysregulated purine metabolism and transcriptomic changes that converge on the PI3K-Akt and phospholipase D signaling pathways. These pathway alterations were associated with lung microbiota dysbiosis, providing new avenues for early biomarker discovery and therapeutic intervention.

Keywords:

Lung microbiota Metabolomics PI3K–Akt signaling pathway Radiation-induced lung injury Transcriptomics

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