ArticleLaboratory investigation; a journal of technical methods and pathology2019
PI3K/Akt pathway-mediated HO-1 induction regulates mitochondrial quality control and attenuates endotoxin-induced acute lung injury.
Article in Laboratory investigation; a journal of technical methods and pathology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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80 citing papers in PubMed, 155 citations in OpenAlex.
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- Liang-Ge-San, a classic Chinese prescription, stimulates macrophage-secreted exosomal miR-21 to ameliorate lipopolysaccharide-induced acute lung injury through the regulation of PTEN/PI3K/AKT signaling.Journal of natural medicines · 2026Article
- Reduced SNHG16 promotes sepsis-induced intestinal injury via the miR-15a-5p/AKT3 axis.BMC gastroenterology · 2026Article
- Integrative multiomics analysis reveals the ameliorative effects of Xiasangju on metabolic dysfunction-associated steatohepatitis.Chinese medicine · 2026Article
- SIRT6 Relieves Acute Lung Injury by Enhancing PGC-1α Expression and Improving Mitochondrial Function.Current molecular medicine · 2026Article
- Deciphering the therapeutic mechanisms of Qingfei Litan prescription in acute lung injury: an integrated framework of UHPLC-MS/MS, systems pharmacology, machine learning, andFrontiers in cellular and infection microbiology · 2026Article
- Immunometabolic reprogramming in sepsis: mechanisms, clinical endotypes, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Bidirectional Regulation of NLRP3 Inflammasome and Mitochondrial Quality Control in Sepsis: Mechanisms and Therapeutic Implications.Mediators of inflammation · 2026Review
- KDM6B induces demethylation of H3K27me3 in MFN1 to modulate aberrant mitophagy in sepsis-induced acute lung injury.Scientific reports · 2025Article
- Metabolic changes in dorsal root ganglia of newborn Wistar rats following LPS exposure to understand mechanisms of critical illness polyneuropathy.Physiological reports · 2025Article
- PROS1/AXL signaling protects mice from lethal influenza infection by inducing M2 macrophage polarization.Acta biochimica et biophysica Sinica · 2025Article
- Computational Modeling of PI3K/AKT Pathway in Bipolar Disorder and Type 2 Diabetes: Implications for Lithium Treatment and Curcumin as a Potential Alternative.International journal of molecular sciences · 2025Article
- EPO-modified bone marrow MSCs alleviate asthma inflammation through enhanced mitochondrial activation and transfer by upregulating HO-1.Molecular medicine (Cambridge, Mass.) · 2025Article
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- The role of mitochondrial dysfunction in the protective effect of ginger derived extracellular vesicles on hepatic stellate cells against cytotoxicity.Molecular and cellular biochemistry · 2025Article
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- Sirt4 Overexpression Modulates the JAK2/STAT3 and PI3K/AKT/mTOR Axes to Alleviate Sepsis-Induced Acute Lung Injury.Cell biochemistry and biophysics · 2025Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sepsis-related acute lung injury (ALI) remains a major cause of mortality in critically ill patients and lacks specific therapy. Mitochondrial dysfunction is involved in the progression of septic lung injury. Mitochondrial dynamics, mitophagy, and biogenesis converge to constitute the assiduous quality control of mitochondria (MQC). Heme oxygenase-1 (HO-1) protects against sepsis-induced ALI through the modulation of mitochondrial dynamics. However, the causal relationship between HO-1 and the general processes of MQC, and their associated cellular pathways in sepsis-related ALI remain ill-defined. Herein, lipopolysaccharide (LPS)-induced ALI in Sprague-Dawley rats together with LPS-induced oxidative injury in RAW264.7 macrophages were used to investigate whether the PI3K/Akt pathway-mediated induction of HO-1 preserves MQC and alleviates septic lung injury. After pretreatment with hemin, a potent inducer of HO-1, LPS-induced cell apoptosis, enhanced mitochondrial fragmentation, and mitochondrial membrane potential damage were significantly reduced in macrophages. In rats, these effects were accompanied by a higher survival rate, less damage to lung tissue, a 28.5% elevation in lung mitochondria MnSOD activity, and a 39.2% increase in respiratory control ratios. Concomitantly, HO-1 induction preserved the dynamic process of mitochondrial fusion/fission (Mfn2, OPA1, Drp1), promoted mitochondrial biogenesis (NRF1, PGC1α, Tfam), and facilitated the key mediators of mitochondrial mitophagy (Parkin, PINK1) at mRNA and protein levels. Notably, LY294002, a PI3K inhibitor, or knockdown of PI3K by small interfering RNA significantly suppressed Akt phosphorylation, attenuated HO-1 induction, and further reversed these beneficial effects evoked by hemin pretreatment in RAW264.7 cells or rats received LPS, indicating a direct involvement of PI3K/Akt pathway. Taken together, our results indicated that HO-1 activation, through PI3K/Akt pathway, plays a critical role in protecting lung from oxidative injury in the setting of sepsis by regulating MQC. HO-1 may therefore be a therapeutic target for the prevention sepsis-related lung injury.
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