ACTA PHARMACOLOGICA SINICA
·
2024
·
IF 6.9
Su Qi,Wang Jing-jing,Ren Jia-yan,Wu Qing,Chen Kun,Tu Kai-hui,Zhang Yu,Leong Sze Wei,Sarwar Ammar,Han Xu,Zhang Mi,Dai Wei-feng,Zhang Yan-min
Parkin ( PARK2 ) deficiency is frequently observed in various cancers and potentially promotes tumor progression. Here, we showed that Parkin expression is downregulated in liver cancer tissues, which correlates with poor patient survival. Parkin deficiency in liver cancer cells promotes migration and metastasis as well as changes in EMT and metastasis markers. A negative correlation exists between TMEFF1 and Parkin expression in liver cancer cells and tumor tissues. Parkin deficiency leads to upregulation of TMEFF1 which promotes migration and metastasis. TMEFF1 transcription is activated by Parkin-induced endogenous TGF-β production and subsequent phosphorylation of Smad2/3 and its binding to TMEFF1 promotor. TGF-β inhibitor and TMEFF1 knockdown can reverse shParkin-induced cell migration and changes of EMT markers. Parkin interacts with and promotes the ubiquitin-dependent degradation of HIF-1α/HIF-1β and p53, which accounts for the suppression of TGF-β production. Our data have revealed that Parkin deficiency in cancer leads to the activation of the TGF-β/Smad2/3 pathway, resulting in the expression of TMEFF1 which promotes cell migration, EMT, and metastasis in liver cancer cells.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RENAL FAILURE
·
2025
·
IF 3
Qiuxia Liao,Zhi Feng,Hairong Lin,Ye Zhou,Xinxin Lin,Xiao Lin,Huichang Zhuo
Impaired autophagy is a key factor in the development of septic acute kidney injury (SAKI). Dexmedetomidine—an α2 adrenergic agonist widely used as a sedative—exerts protective effects in SAKI. However, its correlation with autophagy remains unclear. Consequently, this study aimed to investigate whether the protective effect of dexmedetomidine against SAKI is related to the Pink1/Park2 autophagy pathway. Dexmedetomidine was intraperitonally administered to mice before inducing SAKI with lipopolysaccharide. Subsequently, kidney structure, inflammatory markers, renal function, oxidative stress levels, mitochondrial 16S rRNA expression, autophagy-related protein levels (Pink1, Park2, and Optineurin), and renal cell apoptosis rates were evaluated. Dexmedetomidine reduced inflammatory factors, such as tumor necrosis factor-α, interleukin (IL)-18, IL-6, and IL-1β, and improved kidney function by decreasing serum cystatin C, creatinine, blood urea nitrogen, kidney injury molecule-1, and neutrophil gelatinase-associated lipocalin. Furthermore, it also alleviated kidney tissue damage. Additionally, dexmedetomidine enhanced mitochondrial function; reduced kidney tissue levels of reactive oxygen species, catalase, malondialdehyde, and glutathione; increased superoxide dismutase activity; upregulated mt16S expression; promoted the expression of autophagy-related proteins (Pink1, Park2, and Optineurin); and reduced renal cell apoptosis rates. Notably, all results were statistically significant. Overall, our findings revealed that dexmedetomidine may mitigate inflammation, oxidative stress, and renal dysfunction in mice with SAKI by upregulating the Pink1/Park2-mediated autophagy pathway. These preliminary findings highlight dexmedetomidine’s potential role in SAKI management and warrant further validation in large scale studies.
✓ 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）