Effect of mesenchymal stem cells on FGF23 and disease progression in rats with chronic kidney disease

Objective: Early diagnosis and treatment of chronic kidney injury (CKD) is important for preventing its progression and extrarenal complications. Experimental studies have revealed the potential of mesenchymal stem cells (MSCs) to improve renal function in CKD models. FGF23 is one of the biomarkers suggested for CKD diagnosis. In our study, chronic kidney disease was induced in rats by nephrectomy and MSCs obtained from human placentas were injected into these rats. The therapeutic effects of MSCs were evaluated in the kidneys of rats via FGF23 and Klotho. Method: MSCs were isolated from the amniotic membrane in term placentas. Characterization and guidance experiments were performed for the obtained cells. A CKD model was created by performing a 5/6 nephrectomy model. Protein analyses were performed with Western Blot protocol in the kidney tissues of rats injected with and without MSCs; FGF23 and Klotho analyses were performed at the gene level with Realtime PCR method. Serum FGF23 and α-Klotho levels were determined by ELISA method; Albumin/creatinine ratio and phosphate levels in urine were measured by colorimetric method. Results: In nephrectomy groups, an increase was observed in FGF23 gene and protein expressions compared to control groups. In MSC-administered rats, a decrease in FGF23 expression was determined compared to CKD groups that did not receive MSC. In MSCadministered groups, a decrease in α-Klotho protein and gene levels was determined compared to nephrectomy groups. According to ELISA findings, serum α-Klotho levels were determined to be lower in nephrectomy group tissues compared to stem celladministered groups. Conclusion: FGF23, a measurable biomarker in serum and urine, has an important role in CKD progression. The role of FGF23 against albuminuria formation was evaluated through FGF23 and its coreceptor α-Klotho, and the effect of MSCs on this role was examined. We believe that our study will guide studies investigating CKD progression and the therapeutic effects of MSCs on CKD. Keywords: Mesenchymal stem cell, chronic kidney disease, FGF23, Klotho