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Ziying Yang Xuan Liu Longgang Wang Tao Wang Yueqiu Chen Xiaomei Teng Jingjing Li Lianbo Shao Jie Hui Wenxue Ye Zhenya Shen 《Journal of tissue engineering and regenerative medicine》2020,14(4):588-599
Bone marrow‐derived mesenchymal stromal cells (MSCs) have been wildly applied to cell‐based strategies for tissue engineering and regenerative medicine; however, they have to undergo the senescence process and thus appeared to be less therapeutic effective. HMGA2, a protein belonged to high mobility group A (HMGA) family, exhibits an inverse expression level related to embryonic development and acts as a developmental regulator in stem cell self‐renewal progression. Therefore, we performed senescence‐associated β‐galactosidase (SA‐β‐gal) staining, transwell assay, to examine the changes of MSCs in different stages and then over‐expressed HMGA2 in MSCs by lentivirus transfection. We found the percentage of SA‐β‐gal staining positive cells in MSCs from 24‐month‐old Sprague–Dawley (SD) rats (O‐MSCs) was significantly higher compared with MSCs from 2‐week‐old SD rats (Y‐MSCs), and the expression levels of P21 and P53, two senescence‐related molecules, were also significantly up‐regulated in O‐MSCs than in Y‐MSCs. In contrast, the HMGA2 expression level in O‐MSCs was dramatically down‐regulated in contrast to Y‐MSCs. In additional, the migration ability in O‐MSCs was significantly attenuated than in Y‐MSCs. After successfully over‐expressed HMGA2 in O‐MSCs, the percentage of SA‐β‐gal staining positive cells and the expression levels of P21 and P53 were reduced, and the migration ability was improved compared with O‐MSCs without treatment. Further, mRNA sequencing analysis revealed that overexpression of HMGA2 changed the expression of genes related to cell proliferation and senescence, such as Lyz2, Pf4, Rgs2, and Mstn. Knockdown of Rgs2 in HMGA2 overexpression O‐MSCs could antagonize the protective effect of HMGA2 in the senescence process of O‐MSCs. 相似文献
43.
Haruyoshi Yoshida Naoki Takahashi Takayasu Horiguchi Hiroki Yasuhara Tokuharu Tanaka Yuhao Chen Toshikazu Takasaki Hitokazu Tsukao Michiko Yoshida Satoshi Kawakami Makoto Ohta Hironobu Naiki Satoshi Konishi Isao Ito Masayuki Iwano 《Internal medicine (Tokyo, Japan)》2021,60(24):3927
A 78-year-old man presented with hypercalcemia and renal disease with high serum IgG4 and positive myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA), exhibiting sarcoidosis-like chest findings. A renal biopsy revealed tubulointerstitial nephritis, membranous nephropathy (MN), and sub-capsular lymphoid aggregates without fulfilling the diagnostic criteria of IgG4-related disease or sarcoidosis. Steroid therapy ameliorated the serological and renal abnormalities. After 5 years, following gradual increases in the neutrophil count and upper respiratory infection (URI), necrotizing crescentic glomerulonephritis (NCGN) developed with an increased serum MPO-ANCA level. These results suggest that in the presence of MPO-ANCA in immune senescence, the persistent neutrophil increase with URI may lead to the development of NCGN. 相似文献
44.
Jingang Hou Yeejin Yun Jianjie Xue Byeongmin Jeon Sunchang Kim 《Phytotherapy research : PTR》2020,34(7):1659-1669
Clinical dose of doxorubicin (100 nM) induced cellular senescence and various secretory phenotypes in breast cancer and normal epithelial cells. Herein, we reported the detailed mechanism underlying ginsenoside Rh2‐mediated NF‐κB inhibition, and mitophagy promotion were evaluated by antibody array assay, western blotting analysis, and immunocytostaining. Ginsenoside Rh2 suppressed the protein levels of TRAF6, p62, phosphorylated IKK, and IκB, which consequently inactivated NF‐κB activity. Rh2‐mediated secretory phenotype was delineated by the suppressed IL‐8 secretion. Senescent epithelial cells showed increased level of reactive oxygen species (ROS), which was significantly abrogated by Rh2, with upregulation on SIRT 3 and SIRT 5 and subsequent increase in SOD1 and SOD2. Rh2 remarkably favored mitophagy by the increased expressions of PINK1 and Parkin and decreased level of PGC‐1α. A decreased secretion of IL‐8 challenged by mitophagy inhibitor Mdivi‐1 with an NF‐κB luciferase system was confirmed. Importantly, secretory senescent epithelial cells promoted the breast cancer (MCF‐7) proliferation while decreased the survival of normal epithelial cells demonstrated by co‐culture system, which was remarkably alleviated by ginsenoside Rh2 treatment. These data included ginsenoside Rh2 regulated ROS and mitochondrial autophagy, which were in large part attributed to secretory phenotype of senescent breast epithelial cells induced by doxorubicin. These findings also suggested that ginsenoside Rh2 is a potential treatment candidate for the attenuation of aging related disease. 相似文献
45.
Ching-Pei Chen Kuei-Chuan Chan Hsieh-Hsun Ho Hui-Pei Huang Li-Sung Hsu Chau-Jong Wang 《International journal of medical sciences》2022,19(1):89
Ageing is one of the major risk factors of human diseases, including cancer, diabetes, and cardiovascular disease. Mulberry exhibits a wide range of functions, such as anti-oxidant, anti-inflammation, and anti-diabetes. In this study, we investigated the role of mulberry polyphenol extract (MPE) in K-Ras-induced senescence of smooth muscle cells. Forced expression of K-Ras enhanced senescence of smooth muscle A7r5 cells as shown by the elevation of β-galactosidase activity. Treatment with MPE significantly repressed the Ras, phosphorylated ERK, and β-galactosidase level. MPE triggered the association of cyclins with their corresponding cyclin-dependent protein kinases and hyperphosphorylated retinoblastoma (RB). MPE also down-regulated the levels of K-Ras-induced CDK inhibitors. MPE enhanced the phosphorylated AMP-dependent protein kinase (AMPK) and inducible nitric oxide synthase (iNOS) level in the presence of K-Ras. Pretreatment with either L-NAME or AMPK inhibitor reversed the effects of MPE. In addition, L-NAME and AMPK inhibitor repressed the MPE-induced total and phosphorylated 3-hydroxy-3-methylglutaryl coenzyme A (HMG-Co A) level. MPE repressed K-Ras-induced G0/G1 arrest, whereas L-NAME and AMPK inhibitor blocked the effects of MPE. Our results indicated that MPE recovered the K-Ras-induced senescence of vascular smooth muscle cells through iNOS and AMPK-dependent pathway. Our findings suggested that MPE may prevent ageing-induced atherosclerosis. 相似文献
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48.
Despite advances in cancer therapeutics and the integration of personalized medicine, the development of chemoresistance in many patients remains a significant contributing factor to cancer mortality. Upon treatment with chemotherapeutics, the disruption of homeostasis in cancer cells triggers the adaptive response which has emerged as a key resistance mechanism. In this review, we summarize the mechanistic studies investigating the three major components of the adaptive response, autophagy, endoplasmic reticulum (ER) stress signaling, and senescence, in response to cancer chemotherapy. We will discuss the development of potential cancer therapeutic strategies in the context of these adaptive resistance mechanisms, with the goal of stimulating research that may facilitate the development of effective cancer therapy. 相似文献
49.
目的观察细胞外信号调节激酶1/2(ERK1/2)在血管紧张素Ⅱ(AngⅡ)诱导的内皮细胞中不同时点的表达变化。方法制备AngⅡRPMI1640培养液(10-6 mol/L)培养人脐静脉内皮细胞,采用MTT测定内皮细胞存活率,β-gal染色、细胞周期分析鉴定细胞衰老,透射电子显微镜观察衰老细胞超微结构。细胞免疫化学染色法分析Bcl-2、Bax蛋白表达变化,Western印迹测定磷酸化ERK1/2水平。结果 AngⅡ诱导组存活的细胞数为对照组的〔(81.9±0.04)%,P<0.01)〕;约80%的细胞呈现β-gal阳性染色,流式细胞仪检测细胞周期停滞于G0~G1,证实细胞衰老;透射电子显微镜可见AngⅡ诱导组衰老的细胞体积较大,核形不规则,细胞核染色质浓缩和凝聚。与对照组相比,Bcl-2 mRNA表达呈持续性降低,Bcl-2/Bax比值下降,ERK1/2磷酸化水平于12 h明显增加,24 h达到高峰(P<0.01),36 h下降至稳定,总ERK1/2蛋白水平无明显变化。结论ERK1/2信号转导途径参与AngⅡ诱导内皮细胞衰老的发生、发展过程,并可能通过调控内皮细胞Bcl-2/Bax比值来实现。 相似文献
50.
Microarray analysis of senescent vascular smooth muscle cells: A link to atherosclerosis and vascular calcification 总被引:1,自引:0,他引:1