Characterization of feline nonsteroidal anti-inflammatory drug activated gene-1 (fNAG-1) and its protective function in kidney cells.

BACKGROUND: Domestic cats are susceptible to obesity and chronic renal failure, leading to significant health risks. Nonsteroidal anti-inflammatory drug-activated gene (NAG-1), also known as growth differentiation factor 15 (GDF15), is a member of the transforming growth factor-β superfamily and has been associated with anti-obesity properties and preservation of kidney function. While the NAG-1 sequence has been extensively studied in several species, a comprehensive understanding of feline NAG-1 remains limited. This study aimed to investigate the nucleotide sequence of feline NAG-1 and its biological role in kidney protection through in-vitro experiments. METHODS: The feline NAG-1 cDNA was isolated from the feline uterus, and its sequence was analyzed and compared to sequences from other species, including humans. Expression patterns of feline NAG-1 in various tissues, particularly the liver and kidney, were determined. Furthermore, the effects of different phytochemicals and NSAIDs known to induce NAG-1 expression were assessed using Crandell-Rees Feline Kidney (CRFK) cells. RESULTS: The analysis revealed that feline NAG-1 shares similarities with human NAG-1 and exhibits high expression levels in the liver and kidney of cats. Treatment with tolfenamic acid, quercetin, and resveratrol significantly increased NAG-1 expression in CRFK cells. Subsequently, CRFK cells overexpressing feline NAG-1 were utilized to investigate the functional roles of NAG-1 in feline kidney health. High-content screening analysis demonstrated that NAG-1 overexpression in cat kidney cells enhanced mitochondrial membrane potential, reduced reactive oxygen species (ROS) generation in both whole cells and mitochondria, and downregulated the expression of Bax, a pro-apoptotic protein, under conditions of ROS-induced stress. These findings indicate the renoprotective role of NAG-1. CONCLUSION: This study highlights the significant role of NAG-1 in feline kidney cells, revealing its high expression in the liver and kidney and demonstrating its protective effects on kidney function. These results underscore the potential of NAG-1 as a key factor in kidney protection. Future research should focus on further elucidating the molecular pathways involved and exploring therapeutic strategies to harness NAG-1 for managing obesity-related renal dysfunction in cats.