Klotho microinjection into the RVLM attenuates acute kidney injury via interaction with the cholinergic anti-inflammatory pathway in rats
Background and purpose: The Klotho (Klo) gene, an aging suppressor in rats, accelerates aging when disrupted and extends lifespan when overexpressed. It encodes a transmembrane protein primarily expressed in renal tubules. This study investigated the protective effects of central Klo, both alone and...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Medknow Publications
2025-05-01
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| Series: | Research in Pharmaceutical Sciences |
| Subjects: | |
| Online Access: | https://journals.lww.com/10.4103/RPS.RPS_46_24 |
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| Summary: | Background and purpose:
The Klotho (Klo) gene, an aging suppressor in rats, accelerates aging when disrupted and extends lifespan when overexpressed. It encodes a transmembrane protein primarily expressed in renal tubules. This study investigated the protective effects of central Klo, both alone and in combination with cholinergic anti-inflammatory pathway (CAP) inhibition, against ischemia-reperfusion injury (IRI)- induced acute kidney injury. The current study evaluated the expression of inflammatory and anti-inflammatory genes (including Illb, Tnfa, Tgfb, Trem2, and Il10) in the kidney, alongside plasma levels of creatinine (Cr), blood urea nitrogen (BUN), and signs of acute tubular injury.
Experimental approach:
Klo was microinjected into the rostral ventrolateral medulla, and CAP inhibition was achieved through intraperitoneal administration of mecamylamine (Mec). Real-time RT-PCR and hematoxylin and eosin staining were used for gene expression analysis and histopathological examination, respectively.
Findings/Results:
The results showed elevated Cr and BUN levels, tubular injury, and increased inflammatory gene expression in IRI and IRI + Mec groups, as well as reduced Il10 in the IRI + Mec group. Klo exhibited protective effects. Elevated Tgfb expression was seen in IRI + Klo and IRI + Mec + Klo groups one week post-surgery.
Conclusion and implications:
These findings indicated Klo potential to extend lifespan and protect against age-related diseases, including kidney disease and inflammation, via neural modulation of peripheral immunity. |
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| ISSN: | 1735-5362 1735-9414 |