Klotho microinjection into the RVLM attenuates acute kidney injury interaction with the cholinergic anti-inflammatory pathway in rats.

BACKGROUND AND PURPOSE

The Klotho () 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 and ) 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 in the IRI + Mec group. Klo exhibited protective effects. Elevated 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, neural modulation of peripheral immunity.