NEAT1 functions as a key mediator of BMP2 to promote osteogenic differentiation of renal interstitial fibroblasts

Lay abstract Kidney stones affect one in ten people in the world, and calcium oxalate (CaOx) stones account for 80% of kidney stones. Calcium and oxalate originate from Randall's plaques (RP) which was identified as an anchor for CaOx in renal papilla (parts of the kidney where collecting ducts open to allow urine to flow to the ureter). RP formation shares similarities with bone formation and blood vessel calcification (hardening caused by calcium salt accumulation). Our findings revealed that long non-coding RNA (long nucleotide sequence not made into protein) NEAT1 controlled genes relating to bone formation in kidney cells known as human renal interstitial fibroblasts which are involved in kidney repair processes. This finding implies human renal interstitial fibroblasts might contribute to kidney calcium phosphate deposits prior to RP formation. Collectively, our study provided a new understanding of how NEAT1 might be involved in RP formation by changing the function of osteogenic-like cells in the kidney. Aim: To clarify the mechanism of NEAT1, an aberrantly upregulated lncRNA in Randall's plaques (RP) similar to biomineralization, in mediating osteogenic differentiation of human renal interstitial fibroblasts. Materials & methods: A comprehensive strategy of bioinformatic analysis and experimental verification was performed. Results: BMP2 silence abolished the osteogenic differentiation of human renal interstitial fibroblasts promoted by NEAT1. Mechanically, NEAT1 not only induced the nucleolar translocation of EGR1 binding to BMP2 promotor, but also functioned as a sponge of miR-129-5p in the cytoplasm to promote BMP2 expression. Moreover, there was a positive correlation between NEAT1 and BMP2 expression in RP instead of normal renal papilla. Conclusion: NEAT1 acted as a key mediator of BMP2 to promote human renal interstitial fibroblast osteogenic differentiation, through which NEAT1 might be involved in RP formation.

Automated summary

NEAT1 plays a key role in the formation of kidney stones by altering the function of osteogenic-like cells in the kidney, contributing to the development of Randall's plaques (RP).