Advanced Science
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2025
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IF 14.1
Qian Yuan,Yuting Zhu,Ben Tang,Yaru Xie,Mingcun Hu,Hua Su,Youhua Liu,Chun Zhang
Cellular senescence is a hallmark of aging and the accumulation of senescent cells (SnCs) accelerates the aging process, contributing to aging-related organ disorders. The PRDF1 and RIZ1 homology domain (PRDM) protein exhibits robust transcriptional regulatory activities and governs a wide range of biological processes. However, its roles in cellular senescence remain unclear. Here, this work demonstrates that PRDM16, a member of the PRDM protein family, decreases significantly in multiple organs of aged mice compared to young mice. Global Prdm16 deletion contributes to cellular senescence in various organs, including the kidneys, heart, lungs, hippocampus, stomach, and gut, leading to accelerated aging-related organ injury. Furthermore, tubular-specific Prdm16 deletion aggravates irradiation-induced kidney aging and aging-related kidney diseases in irradiated mice subjected to ischemia-reperfusion surgery. Exogenous PRDM16 gene delivery by lentivirus effectively attenuates cellular senescence in vitro and in vivo. Mechanistically, PRDM16 improves glutathione metabolism and inhibits oxidative DNA damage, which is a driving force of senescence. Specifically, PRDM16 upregulates the transcription of glutathione S-transferase mu 1 (GSTM1) by binding to its promoter region. Transfection with GSTM1 reverses PRDM16 deficiency-induced cellular senescence and kidney aging. Collectively, these results provide a potential target for the investigation of anti-aging therapies.
研究领域:
分子生物学
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老年学
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肾脏病学
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氧化应激
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遗传学
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转化医学
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信号转导
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产品关联
DOI
PubMed
高影响因子
CELLULAR AND MOLECULAR LIFE SCIENCES
·
2026
·Vol. 83
·期 1
·211
·
IF 6.5
Feng Yuqing,Li Zhou,Lu Jinfang,Peng Xujun,He Zijin,Jia Ao,Bao Yaohui,Zheng Qiang,Xu Xuan,Ma Yuxuan,Zou Chun,Li Huiling,Zhang Dongshan
Ischemia-reperfusion (I/R) injury represents a prevalent etiology of permanent vision loss across multiple ocular pathologies. Apoptotic death and inflammation of retinal ganglion cells (RGCs) induced by I/R injury constitutes a major contributor to visual dysfunction. Nevertheless, the molecular mechanisms that initiate the apoptotic and inflammation cascade in RGCs remain largely uncharacterized. Recent investigations have demonstrated that PRD1-BF1-RIZ1 homeodomain protein 16 (PRDM16) attenuates renal cell death in acute kidney injury. However, its specific function and regulatory mechanisms in I/R-induced RGCs apoptosis and inflammation remain poorly understood. Here, we demonstrate that PRDM16 expression is markedly upregulated in RGCs and mouse retinas following I/R injury. Functionally, PRDM16 overexpression markedly attenuates I/R-induced RGCs apoptosis and inflammation, while its RGC-specific deletion exacerbates retinal structural damage and functional deficits. Mechanistically, PRDM16 binds to the Ribosomal Protein L5 (RPL5) promoter and enhances its transcription. Additionally, co-immunoprecipitation assays revealed a physical association between PRDM16 and RPL5. This PRDM16-mediated enrichment of RPL5 subsequently suppresses p53 signaling, leading to the upregulation of FCGR2B. Increased FCGR2B, in turn, inhibits the overactivation of MAPK (p38 and JNK) signaling and the assembly of the NLRP3/IL-1β inflammasome axis. In conclusion, these findings identify PRDM16 as a critical endogenous protective regulator that alleviates retinal I/R-induced damage through modulation of the RPL5/p53/FCGR2B/MAPK axis. Targeting PRDM16 regulatory networks may therefore represent a promising therapeutic strategy for retinal ischemic diseases. Graphical abstract Ischemia–reperfusion injury induces apoptosis and inflammation in RGCs. PRDM16 is upregulated in response to ischemic stress and exerts a protective effect by transcriptionally activating RPL5. Increased RPL5 suppresses p53 expression, leading to upregulation of FCGR2B and subsequent inhibition of p38 MAPK and JNK signaling. Additionally, co-immunoprecipitation assays reveal a physical association between PRDM16 and RPL5. This regulatory cascade attenuates caspase-3 activation and inflammatory mediator (NLRP3 and IL-1β) expression, ultimately protecting RGCs from ischemia-induced injury. The alternative text for this image may have been generated using AI.
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DOI
高影响因子
Food & Function
·
2021
·Vol. 12
·期 14
·6490-6501
·
IF 5.396
Ao Sun,Xiaoqin Hu,Huijian Chen,Yulan Ma,Xiyue Yan,Dangsheng Peng,Jie Ping,Youe Yan
Ursolic acid (UA) shows an effect on obesity and related metabolic diseases, but its mechanism of action remains unclear. We found that UA clearly reduced the body weight and adipose tissue mass and improved the glucose tolerance and insulin sensitivity in obese male mice. UA treatment significantly reduced the volume and weights of the epididymal white adipose tissue (eWAT) and inguinal subcutaneous white adipose tissue (igSWAT) of HFD-fed mice, respectively. UA also decreased the expression of genes involved in adipocyte differentiation and lipogenesis in igSWAT. Real-time PCR and immunohistochemistry showed that the expression of beiging-related genes 4-1BB factor (CD137), T-box transcription factor 1 (TBX1), and transmembrane protein 26 (TMEM26) were significantly increased in the UA treatment group. UA treatment significantly reduced the weight of gastrocnemius muscle (GM) and lipid droplets in the GM. UA treatment significantly upregulated the expression of PR domain-containing 16 (PRDM16), peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), and fibronectin type 3 domain-containing protein 5 (FNDC5) in GM and igSWAT. UA also stimulated irisin secretion in the serum. In conclusion, these results indicate that UA plays an anti-obesogenic role by increasing the secretion of irisin and promoting the beiging of WAT.
研究领域:
药理学
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代谢
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肥胖研究
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
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2023
·
IF 5.6
Wenkai Zhang,Li Kong,Zhen Zhong,Lezhen Lin,Jingen Li,Guodong Zheng
To investigate the molecular mechanism of short chain fatty acids (SCFAs) on promoting fatty acid β-oxidation and browning in 3T3-L1 adipocytes. SCFAs significantly reduced lipid accumulation in 3T3-L1 adipocytes. In addition, via increasing the expression of Tfam and Nrf1, SCFAs enhanced mitochondrial biogenesis. According to the results of qPCR analysis, the expression levels of fatty acid β-oxidation genes ( PPARα , CPT1α , ACOX1 ) were up-regulated by SCFAs. Moreover, SCFAs treatment increased the genes and proteins expression of brown adipocyte-specific factors such as PRDM16, PGC-1α, and UCP-1, as well as up-regulated the genes expression of beige adipocytes markers ( Tmem26 , Tbx1 , CD137, and Cited1) . Furthermore, the effects of β3-AR and AMPK antagonist were reversed by SCFAs. In conclusion, SCFAs promote fat β-oxidation and browning of adipocytes through β3-AR/AMPKα signaling pathway, thereby reducing fat accumulation in 3T3-L1 adipocytes. Therefore, SCFAs may be a helpful supplement to combat obesity.
研究领域:
分子生物学
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细胞生物学
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代谢
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营养学
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DOI
高影响因子
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