High-dose SFRP2 attenuates fibrosis and promotes angiogenesis via Wnt signaling modulation in diabetic erectile...

This study investigated whether high-dose secreted frizzled-related protein 2 (SFRP2) attenuates fibrosis and improves endothelial function under diabetic-like conditions. Diabetic erectile dysfunction (ED) is marked by progressive corpus cavernosum fibrosis and endothelial dysfunction, driven partly by dysregulated Wnt signaling. Primary human corpus cavernosum fibroblasts were stimulated with bone morphogenetic protein 1 (BMP1, 50 ng/mL) or high glucose (HG, 30 mM), with or without SFRP2, and fibrotic responses were assessed by Western blot for collagen I/IV and Wnt markers. Endothelial dysfunction was modeled in human umbilical vein endothelial cells (HUVECs) using tube formation, proliferation, and apoptosis assays. BMP1 and HG increased SFRP2 expression and collagen accumulation, mimicking low-dose SFRP2 effects. In contrast, high-dose SFRP2 (20 µM) suppressed fibrosis, reducing collagen I/IV expression by 40-62 % and downregulating Wnt3a and Wnt5a/b by 40-66 %. High-dose SFRP2 also enhanced angiogenesis and reduced apoptosis by ∼50 % under HG stress. These findings suggest that high-dose SFRP2 mitigates fibrosis and promotes angiogenesis, likely through inhibition of canonical Wnt signaling. As all results were obtained from in vitro models, in vivo studies are required. Future work will evaluate high-dose SFRP2 in rodent diabetic ED models to determine therapeutic feasibility, safety, and translational potential.