2. Academic Validation
  3. METTL3-mediated m6A modification of CD36: Implications for glucose metabolism and inflammatory dysregulation in follicles of polycystic ovary syndrome

METTL3-mediated m6A modification of CD36: Implications for glucose metabolism and inflammatory dysregulation in follicles of polycystic ovary syndrome

  • Int Immunopharmacol. 2024 Dec 25;143(Pt 1):113327. doi: 10.1016/j.intimp.2024.113327.
Linglin Weng 1,  Qi Zhu 2,  Yu Xiang 3,  Tingting Cao 3,  Jieyu Cai 1,  Na Liang 4,  Xiaoqi Hong 2,  Mingrui Xue 4,  Hongshan Ge 5
Affiliations

Affiliations

  • 1 Graduate School, Nanjing University of Chinese Medicine, Nanjing 210023, China; Reproduction Medicine Centre, Nanjing Medical University Affiliated Taizhou People's Hospital, Taizhou 225300, China.
  • 2 Reproduction Medicine Centre, Nanjing Medical University Affiliated Taizhou People's Hospital, Taizhou 225300, China; Graduate School, Nanjing Medical University, Nanjing 211166, China.
  • 3 Reproduction Medicine Centre, Nanjing Medical University Affiliated Taizhou People's Hospital, Taizhou 225300, China.
  • 4 Reproduction Medicine Centre, Nanjing Medical University Affiliated Taizhou People's Hospital, Taizhou 225300, China; Graduate School, Dalian Medical University, Dalian 116044, China.
  • 5 Graduate School, Nanjing University of Chinese Medicine, Nanjing 210023, China; Reproduction Medicine Centre, Nanjing Medical University Affiliated Taizhou People's Hospital, Taizhou 225300, China; Graduate School, Nanjing Medical University, Nanjing 211166, China; Graduate School, Dalian Medical University, Dalian 116044, China. Electronic address: hongshange@njmu.edu.cn.
PMID: 39395382 DOI: 10.1016/j.intimp.2024.113327
Abstract

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder that affects women of reproductive age and is characterized by menstrual irregularities, metabolic imbalances and infertility. The pathogenesis of PCOS is complex and not fully understood, and chronic inflammation and Insulin resistance are implicated in its progression. In this study, we investigated the role of m6A methylation, an important epigenetic modification, in the pathogenesis of PCOS. Using methylated RNA immunoprecipitation Sequencing (MeRIP-seq) and RNA Sequencing (RNA-seq), we mapped the m6A methylation profile in granulosa cells from patients with PCOS and identified a significant regulatory effect on gene expression. CD36 is a novel m6A-regulated gene that may facilitate the progression of PCOS. We demonstrated that METTL3, an m6A methyltransferase, modulated CD36 expression and influenced glucose metabolism and inflammatory responses in PCOS. Employing KGN cells as a model of Insulin resistance, we observed that CD36 knockdown ameliorated the impaired glucose uptake and significantly reduced the production of pro-inflammatory cytokines. These findings are consistent with the results of CD36 inhibition in a mouse model of PCOS, indicating a role of CD36 in modulating the disease phenotype. Our study delineates a previously unrecognized epigenetic mechanism involving m6A methylation in PCOS, highlighting the potential of targeting the METTL3-CD36 axis as a therapeutic strategy for managing ovarian inflammation and metabolic dysregulation in patients with PCOS.

Keywords

CD36; Inflammation; Insulin resistance; METTL3; Polycystic ovary syndrome; m(6)A methylation.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z