NEAT1 Functions as a Key Mediator of BMP2 to promote osteogenic differentiation of renal interstitial fibroblasts

Abstract

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.

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.

Keywords::

• BMP2
• NEAT1
• osteogenic differentiation
• Randall’s plaques
• renal interstitial fibroblasts

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2021-0212

Author contributions

Z Zhu: literature search; experimental studies; data analysis; manuscript preparation. X Zhang: sample collection; experimental studies. Y Jiang: experimental studies. S Ruan: sample collection; experimental studies. F Huang: sample collection; experimental studies. H Zeng: experimental studies. M Liu: experimental studies. W Xia: experimental studies. F Zeng: data analysis; statistical analysis. J Chen: data analysis; statistical analysis. Y Cui: concept and design; manuscript editing; manuscript review. H Chen: concept and design; manuscript review. All authors read and approved the final manuscript.

Financial & competing interests disclosure

This work was supported by the National Natural Science Foundation of China (81770705 to Hequn Chen; 82000761 to Y Cui) and Natural Science Foundation of Hunan Province (2017JJ3482 to X Zhang). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval granted by Xiangya Hospital Ethics Committee (proof number: 201603035) and have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Data sharing statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (81770705 to Hequn Chen; 82000761 to Y Cui) and Natural Science Foundation of Hunan Province (2017JJ3482 to X Zhang). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.