Is activated Yes-Associated Protein (YAP) associated with renal damage in type2 diabetic nephropathy?

BACKGROUND: Type 2 diabetic nephropathy (DN) is a major cause of end-stage renal disease, characterized by progressive renal fibrosis. The Hippo signaling pathway, particularly through Yes Associated Protein (YAP), has been implicated in the fibrotic response. However, limited studies have examined YAP expression, along with its coactivator Transcriptional Enhanced Associate Domain (TEA Domain - TEAD) and downstream effector Connective Tissue Growth Factor (CTGF), in human renal tissue. This study explores their role by evaluating the immunohistochemical expression of YAP, TEAD, and CTGF in patients with type 2 diabetic nephropathy. METHODS: A total of 33 biopsy-proven cases of pure Type 2 diabetic nephropathy were analysed. Immunohistochemistry (IHC) was performed to assess the expression of YAP, TEAD, and CTGF, with results graded based on staining intensity and percentage of positive cells. Clinicopathological parameters were documented, while fibrosis was assessed using Picrosirus red stain and Masson's Trichrome stain before subjecting them to morphometry using Qu Path software. RESULTS: Our results showed that increased expression of YAP, TEAD, and CTGF was associated with more advanced histological classes of diabetic nephropathy. A strong correlation was found between higher expression levels and impaired renal function, indicated by increased serum creatinine and blood urea nitrogen (BUN) levels. Morphometric analysis further supported the role of these markers in causing increased fibrosis, with higher expression levels correlating with increased fibrotic changes. CONCLUSION: This study suggests that YAP, TEAD, and CTGF expression, assessed by intensity and percentage of positive staining, may serve as biomarkers for disease severity in diabetic nephropathy and potential targets for therapeutic intervention.