Diabetes Mellitus is a major global health problem with an increasing worldwide prevalence, currently estimated to affect more than 10% of global population. Chronic hyperglycaemia promotes inflammation, oxidative stress and tissue injury, contributing to the development of kidney disease. FOSL1/FRA1 is a member of the AP-1 transcription factor family involved in cellular stress and inflammatory responses. Increased kidney expression of AP-1 transcription factor components has been reported in acute kidney injury (AKI). However, its role in diabetes remains poorly understood.
In a mouse model of hyperglycemia (streptozotocin-induced diabetes), kidney Fosl1 was overexpressed (mRNA and protein expression). Proximal tubular cell-specific Fosl1 knockout mice (Fosl1Δtub) developed earlier, and more severe hyperglycaemia compared to wild-type diabetic animals. Moreover, Fosl1Δtub mice showed increased expression of inflammatory mediators and NADPH oxidase family members, while nephroprotective factors levels, such as Klotho and PGC1α, were lower than in wild-type diabetic animals. This was also associated with a trend toward more severe inflammatory cell infiltration in renal tissue.
Overall, these findings suggest a potential involvement of tubular Fosl1 in systemic metabolic regulation and in the renal response to experimental diabetes and support further studies to clarify its contribution to inflammatory and oxidative stress pathways during diabetic kidney injury.