SRPK1 is a significant factor in driving the progression of diabetic kidney fibrosis

Diabetic nephropathy leads to renal fibrosis via excessive ECM accumulation. Current therapies lack specificity, highlighting the need to identify targets like SRPK1, whose role in diabetic kidney fibrosis remains unclear. We investigated SRPK1's function using a streptozotocin-induced diabetic nephropathy mice model and administered the selective SRPK1 inhibitor SRPIN340. Histological, biochemical, and molecular analyses were performed to assess ECM deposition, renal function, and fibrotic marker expression. Additionally, Western blotting and immunohistochemistry were utilized to explore the involvement of the NF-κB/NLRP3 signaling pathway. SRPK1 expression was significantly elevated in fibrotic kidneys, correlating with increased ECM components (collagen I/III, fibronectin) and reduced renal function. SRPIN340 treatment markedly alleviated ECM accumulation, improved glomerular filtration rate, and suppressed fibrotic markers (α-SMA, TGF-β). Mechanistically, SRPK1 activation promoted NF-κB/NLRP3 pathway activation, leading to inflammatory cytokine release (IL-1β, TNF-α) and fibrosis. Inhibition of SRPK1 via SRPIN340 abrogated these effects, suggesting a causal role for SRPK1 in fibrotic progression. SRPK1 activates NF-κB/NLRP3 pathway, promoting ECM synthesis and inflammation in diabetic nephropathy; SRPIN340 reduces fibrosis, highlighting SRPK1 as a therapeutic target.