Cytosolic calreticulin inhibits microwave radiation-induced microvascular endothelial cell injury through the integrin-focal adhesion kinase pathway.

Abstract

OBJECTIVE: To determine the effects of cytosolic CRT on MR-induced MMEC injury, and the underlying mechanism. METHODS: MMECs were randomized into eight groups: control, AdCRT (infected with pAdCMV/V5-DEST-CRT adenovirus), stCRT (transfected with rCRT-siRNAs), Mock (transfected with scrambled siRNAs), MR (exposed to MR for six minutes), AdCRT + MR, stCRT + MR, and Mock + MR. The magnitude of cell injury were assessed by Annexin V-PI staining, LDH activity in culture medium, MMEC migration ability, ultrastructure and cytoskeletal stability. Subcellular colocalization of CRT and ConA or integrin were evaluated by immunocytochemistry. The mRNA and protein expression levels of target genes were examined by qRT-PCR and western blotting, respectively. RESULTS: MR-induced cytotoxicity was dose-dependent. Overexpression of cytosolic CRT suppressed MR injury, shown as decreased cell apoptosis, reduced LDH activity, enhanced cell migration capability, and maintenance of ultrastructure and cytoskeleton integrity. Conversely, CRT deficiency aggravated MR-induced injury. Exposure of AdCRT MMECs to MR promoted membrane translocation of CRT and the interaction of CRT-integrin-α. Correlation analysis revealed that integrin-α expression or FAK phosphorylation was positively associated with cytosolic CRT expression. CONCLUSIONS: Cytosolic CRT inhibits MR-induced MMEC injury through activation of the integrin-FAK pathway.

AI evidence extraction

Main findings

Microwave radiation (MR) induced dose-dependent cytotoxicity in mouse microvascular endothelial cells (MMECs). Overexpression of cytosolic calreticulin (CRT) reduced MR-associated injury markers (lower apoptosis and LDH activity) and improved migration and structural integrity, while CRT deficiency aggravated MR-induced injury. In AdCRT cells exposed to MR, CRT translocated to the membrane and interacted with integrin-α; integrin-α expression and FAK phosphorylation were positively associated with cytosolic CRT expression.

Outcomes measured

• MMEC injury/cytotoxicity
• apoptosis (Annexin V-PI)
• LDH activity in culture medium
• cell migration ability
• ultrastructure
• cytoskeletal stability
• CRT membrane translocation
• CRT-integrin-α interaction/colocalization
• integrin-α expression
• FAK phosphorylation

Limitations

• In vitro cell model; findings may not generalize to in vivo or human exposures.
• Exposure parameters beyond duration (e.g., frequency, SAR/power density) are not provided in the abstract.
• Sample size and replication details are not reported in the abstract.

{
    "study_type": "in_vitro",
    "exposure": {
        "band": null,
        "source": "microwave radiation",
        "frequency_mhz": null,
        "sar_wkg": null,
        "duration": "six minutes"
    },
    "population": null,
    "sample_size": null,
    "outcomes": [
        "MMEC injury/cytotoxicity",
        "apoptosis (Annexin V-PI)",
        "LDH activity in culture medium",
        "cell migration ability",
        "ultrastructure",
        "cytoskeletal stability",
        "CRT membrane translocation",
        "CRT-integrin-α interaction/colocalization",
        "integrin-α expression",
        "FAK phosphorylation"
    ],
    "main_findings": "Microwave radiation (MR) induced dose-dependent cytotoxicity in mouse microvascular endothelial cells (MMECs). Overexpression of cytosolic calreticulin (CRT) reduced MR-associated injury markers (lower apoptosis and LDH activity) and improved migration and structural integrity, while CRT deficiency aggravated MR-induced injury. In AdCRT cells exposed to MR, CRT translocated to the membrane and interacted with integrin-α; integrin-α expression and FAK phosphorylation were positively associated with cytosolic CRT expression.",
    "effect_direction": "harm",
    "limitations": [
        "In vitro cell model; findings may not generalize to in vivo or human exposures.",
        "Exposure parameters beyond duration (e.g., frequency, SAR/power density) are not provided in the abstract.",
        "Sample size and replication details are not reported in the abstract."
    ],
    "evidence_strength": "low",
    "confidence": 0.7800000000000000266453525910037569701671600341796875,
    "peer_reviewed_likely": "yes",
    "keywords": [
        "microwave radiation",
        "microvascular endothelial cells",
        "calreticulin",
        "integrin",
        "focal adhesion kinase",
        "apoptosis",
        "LDH",
        "cell migration"
    ],
    "suggested_hubs": []
}

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