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Updated: Jan 4, 2026
Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
METTL14-dependent m6A regulates vascular calcification induced by indoxyl sulfate
Jing Chen1, Yichun Ning1, Han Zhang1
1Department of Nephrology, Zhongshan Hospital, Fudan University, China; Shanghai Medical Center of Kidney, China; Shanghai Institute of Kidney and Dialysis, Shanghai, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai, China; Hemodialysis quality control center of Shanghai, China.
Aims:
Although the functional importance of N6-methyladenosine (m6A) in various fundamental bioprocesses are well known, its effect on vascular calcification is not well studied. We investigated the role of methyltransferase-like 14 (METTL14), an m6A methylase, in vascular calcification.
Main Methods:
We used clinical human samples as well as rat models and primary human artery smooth muscle cell (HASMC) cultures to study the functional role of m6A and METTL14 in vascular calcification and in HASMCs. We modulated the expression of METTL14 using siRNAs (in vitro) to study its function in regulating HASMCs m6A, osteoblasts induced by indoxyl sulfate. We performed the MeRIP-qPCR assays to map and validate m6A in individual transcripts, controls, and calcific HASMCs.
Key Findings:
We discovered that the METTL14 expression increases in calcific arteries and in HASMCs induced by indoxyl sulfate, thereby increasing the m6A level in RNA and decreasing the vascular repair function. Decreasing the expression of METTL14 in calcified arteries attenuated the indoxyl sulfate-induced increase in m6A and decrease in HASMCs calcification. We performed the methylation activity of METTL14, which selectively methylates vascular osteogenic transcripts, thereby promoting their degradation and improving their protein expression induced by indoxyl sulfate. Moreover, we demonstrated that the METTL14 de-expression in HASMCs models of calcification decreased the calcification and enhanced the vascular repair function.
Significance:
Collectively, our results demonstrated the functional importance of METTL14-dependent vascular m6A methylome in vascular functions during calcification and provided a novel mechanistic insight to the therapeutic mechanisms of METTL14.
Insights
Methyltransferase-like 14 (METTL14) promotes vascular calcification by increasing RNA N6-methyladenosine (m6A) levels. Reducing METTL14 expression in smooth muscle cells enhances vascular repair and decreases calcification.
Area of Science:
- Molecular Biology
- Epigenetics
- Cardiovascular Research
Background:
- N6-methyladenosine (m6A) is crucial for cellular processes, but its role in vascular calcification remains unclear.
- Methyltransferase-like 14 (METTL14) is a key enzyme in m6A methylation.
Purpose of the Study:
- To investigate the role of METTL14 in vascular calcification.
- To elucidate the mechanisms by which METTL14 influences vascular smooth muscle cell function.
Main Methods:
- Utilized human samples, rat models, and primary human artery smooth muscle cell (HASMC) cultures.
- Modulated METTL14 expression using siRNAs and performed MeRIP-qPCR assays.
- Assessed m6A levels, calcification, and vascular repair functions in HASMCs.
Main Results:
- METTL14 expression and m6A levels were elevated in calcified arteries and HASMCs treated with indoxyl sulfate.
- Downregulation of METTL14 reduced m6A levels, attenuated calcification, and improved vascular repair.
- METTL14 selectively methylates osteogenic transcripts, promoting their degradation and enhancing protein expression.
Conclusions:
- METTL14 plays a significant role in vascular calcification through its regulation of the m6A methylome.
- METTL14 represents a potential therapeutic target for vascular calcification.
