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Objective <p>To investigate the underlying mechanism of NLRP3 in the pathogenesis of parathyroid hyperplasia.</p> Methods <p>Parathyroid glands (PGs) (<i>n</i> = 35) were obtained from 10 maintenance hemodialysis patients undergoing parathyroidectomy. A secondary hyperparathyroidism (SHPT) model was induced in rats by 5/6 nephrectomy followed by a high‑phosphate diet. Serum levels of calcium, phosphorus, creatinine, blood urea nitrogen (BUN), and intact parathyroid hormone (PTH) were measured. The expression of IGF2BP3 and NLRP3 was evaluated using quantitative reverse‑transcription polymerase chain reaction and Western blotting. NLRP3 mRNA stability was examined through RNA decay assays, and its translation was assessed by polysome profiling. RNA immunoprecipitation was performed to confirm the binding of IGF2BP3 to NLRP3 mRNA, while N⁶‑methyladenosine (m⁶A) modification levels in NLRP3 mRNA were measured via m⁶A‑RIP.</p> Results <p>NLRP3 expression was detected in pathological parathyroid tissues from chronic kidney disease patients with SHPT. Compared with less severe diffuse hyperplastic nodules, NLRP3 expression was significantly higher in nodular hyperplastic PG tissues. In SHPT rats, both IGF2BP3 and NLRP3 were upregulated in PG tissues. Knockdown of IGF2BP3 or NLRP3 reduced serum PTH levels and suppressed PG hyperplasia in SHPT rats. IGF2BP3 regulated NLRP3 expression in PGs through m⁶A‑dependent mechanisms by modulating NLRP3 mRNA stability and translation. NLRP3 overexpression reversed the phenotypic effects of IGF2BP3 knockdown in PG tissues of SHPT rats.</p> Conclusion <p>IGF2BP3 enhances NLRP3 mRNA stability and translation via m⁶A modification, thereby aggravating SHPT and parathyroid hyperplasia.</p>

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IGF2BP3 mediates the mRNA upregulation of NLRP3 to promote parathyroid cell proliferation in chronic kidney disease via an m⁶A-dependent manner

  • 期刊论文

  • 发表日期：

    2026年7月10日

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  • Sen Kan,
  • BianJie Zhao,
  • Long Miao,
  • ZhengJie Han,
  • QinJun Li,
  • Yu Wu,
  • Ling Wang

摘要

Objective

To investigate the underlying mechanism of NLRP3 in the pathogenesis of parathyroid hyperplasia.

Methods

Parathyroid glands (PGs) (n = 35) were obtained from 10 maintenance hemodialysis patients undergoing parathyroidectomy. A secondary hyperparathyroidism (SHPT) model was induced in rats by 5/6 nephrectomy followed by a high‑phosphate diet. Serum levels of calcium, phosphorus, creatinine, blood urea nitrogen (BUN), and intact parathyroid hormone (PTH) were measured. The expression of IGF2BP3 and NLRP3 was evaluated using quantitative reverse‑transcription polymerase chain reaction and Western blotting. NLRP3 mRNA stability was examined through RNA decay assays, and its translation was assessed by polysome profiling. RNA immunoprecipitation was performed to confirm the binding of IGF2BP3 to NLRP3 mRNA, while N⁶‑methyladenosine (m⁶A) modification levels in NLRP3 mRNA were measured via m⁶A‑RIP.

Results

NLRP3 expression was detected in pathological parathyroid tissues from chronic kidney disease patients with SHPT. Compared with less severe diffuse hyperplastic nodules, NLRP3 expression was significantly higher in nodular hyperplastic PG tissues. In SHPT rats, both IGF2BP3 and NLRP3 were upregulated in PG tissues. Knockdown of IGF2BP3 or NLRP3 reduced serum PTH levels and suppressed PG hyperplasia in SHPT rats. IGF2BP3 regulated NLRP3 expression in PGs through m⁶A‑dependent mechanisms by modulating NLRP3 mRNA stability and translation. NLRP3 overexpression reversed the phenotypic effects of IGF2BP3 knockdown in PG tissues of SHPT rats.

Conclusion

IGF2BP3 enhances NLRP3 mRNA stability and translation via m⁶A modification, thereby aggravating SHPT and parathyroid hyperplasia.