Fig. 7
Schematic illustration of the possible involvement of OLMALINC/OCT4/BMP2 axis mediated osteogenic-like differentiation of human renal interstitial fibroblasts (hRIFs) in Randall’s Plaque formation. A A normal renal papilla in which Henle loop, hRIFs, and epithelial cells are shown. B HRIFs adopt an osteogenic-like phenotype and calcium phosphate (CaP) deposits are formed in renal interstitium of renal papilla. C CaP deposits aggregate and impair the musca of renal papilla, leading to RP formation as an anchor for calcium oxalate (CaOx) crystals to induce stone formation. D, E The molecular mechanism in the osteogenic-like differentiation of hRIFs based our findings. OCT4 bound to the sequences (AAATGCAAATT) in BMP2 promoter where the POU-specific domain (POUS) and the POU homeodomain (POUHD) recognized and bound to ATGC and AAAT respectively, and decreased the DNA methylation of BMP2 promoter to transcriptionally promote BMP2 expression. OLMALINC stabilized OCT4 to enhance osteogenic-like differentiation of hRIFs via disrupting its ubiquitination. This illustration was created with BioRender.com