ZOOLOGICAL RESEARCH
·
2025
·Vol. 46
·期 3
·722
·
IF 4.7
Chun-Xue Zhou,Si-Qi Wang,Ji-Yu Zhang,Xing Du,Qi-Fa Li
NORHA, a long non-coding RNA (lncRNA), serves as a key inducer of follicular atresia in sows by triggering granulosa cells (GCs) apoptosis. However, its regulation by N6-methyladenosine (m6A)—the most abundant RNA modification—remains unresolved. This study identified NORHA as a functional target of the m6A reader HNRNPA2B1 in sow GCs (sGCs). Transcriptome-wide mapping of RNA modification sites revealed extensive m6A enrichment on NORHA, with HNRNPA2B1 binding directly to the transcript and enhancing its stability via modification of multiple m6A sites, including A261, A441, and A919. HNRNPA2B1 suppressed 17β-estradiol (E2) biosynthesis and promoted sGC apoptosis by activating the NORHA-FoxO1 axis. FoxO1 subsequently repressed expression of cytochrome P450 family 19 subfamily A member 1 (CYP19A1), which encodes the enzyme essential for E2 biosynthesis. Additionally, HNRNPA2B1 functioned as a critical mediator of METTL3-dependent m6A modification, modulating NORHA expression and activity in sGCs. This study highlights an important m6A-dependent regulatory mechanism governing NORHA expression in sGCs.
研究领域:
生殖生物学
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RNA表观遗传学
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分子生殖学
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长非编码RNA
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卵巢生理学
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细胞凋亡
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Death Discovery
·
2023
·Vol. 9
·期 1
·1-11
·
IF 7
Yang Liu,Du Xing,Wang Siqi,Lin Chenggang,Li Qiqi,Li Qifa
Follicular atresia triggered by granulosa cell (GC) apoptosis severely reduces female fertility and accelerates reproductive aging. GC apoptosis is a complex process regulated by multiple factors, regulatory axes, and signaling pathways. Here, we report a novel, small regulatory network involved in GC apoptosis and follicular atresia. miR-187, a miRNA down-regulated during follicular atresia in sows, maintains TGFBR2 mRNA stability in sow GCs by directly binding to its 5’-UTR. miR-187 activates the transforming growth factor-β (TGF-β) signaling pathway and suppresses GC apoptosis via TGFBR2 activation. NORHA, a pro-apoptotic lncRNA expressed in sow GCs, inhibits TGFBR2-mediated activation of the TGF-β signaling pathway by sponging miR-187. In contrast, NORFA, a functional lncRNA associated with sow follicular atresia and GC apoptosis, enhances miR-187 and TGFBR2 expression by inhibiting NORHA and activating NFIX. Our findings define a simple regulatory network that controls GC apoptosis and follicular atresia, providing new insights into the mechanisms of GC apoptosis, follicular atresia, and female fertility.
研究领域:
生殖生物学
·
分子生物学
·
内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2023
·
IF 6.2
Xiong Xiao,Yuchu Yang,Yushang Lai,Ziwei Huang,Chenxi Li,Shaojie Yang,Chuan Niu,Liping Yang,Li Feng
Light-based three-dimensional (3D) bioprinting has been widely studied in tissue engineering. Despite the fact that free-radical chain polymerization-based bioinks like hyaluronic acid methacrylate (HAMA) and gelatin methacryloyl (GelMA) have been extensively explored in 3D bioprinting, the thiol–ene hydrogel system has attracted increasing attention for its ability in building hydrogel scaffolds in an oxygen-tolerant and cell-friendly way. Herein, we report a superfast curing thiol–ene bioink composed of norbornene-modified hyaluronic acid (NorHA) and thiolated gelatin (GelSH) for 3D bioprinting. A new facile approach was first introduced in the synthesis of NorHA, which circumvented the cumbersome steps involved in previous works. Additionally, after mixing NorHA with macro-cross-linker GelSH, the customized NorHA/GelSH bioinks exhibited fascinating superiorities over the gold standard GelMA bioinks, such as an ultrafast curing rate (1–5 s), much lowered photoinitiator concentration (0.03% w/v), and flexible physical performances. Moreover, the NorHA/GelSH hydrogel greatly avoided excess ROS generation, which is important for the survival of the encapsulated cells. Last, compared with the GelMA scaffold, the 3D-printed NorHA/GelSH scaffold not only exhibited excellent cell viability but also guaranteed cell proliferation, revealing its superior bioactivity. In conclusion, the NorHA/GelSH system is a promising candidate for 3D bioprinting and tissue engineering applications.
研究领域:
组织工程
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生物打印
·
生物材料
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材料科学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）