ANALYTICAL CHEMISTRY
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2025
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IF 6.7
Wendi Wang,Qing Han,Tianwei Wang,Jian Liu,Qingbin Ni,Jingyi Sun,Ying Wang,Baoliang Sun
Ischemic stroke (IS) has a high mortality rate. Multiplexed detection of IS core biomarkers is of great significance to early diagnosis and personalized treatment of IS patients. Whether pericytes, a key component of the neurovascular unit and blood-brain barrier located on the capillary wall, could serve as a promising biomarker for IS is to be explored. Herein, we observed a significant upregulation of inflammatory and apoptotic factors, such as MMP9, in pericytes subjected to in vitro ischemia. By transfecting pericytes with ASK1-shRNA to inhibit ASK1 expression, we noted reduced levels of inflammatory and apoptotic markers, including MMP9, as well as enhanced pericyte contraction and migration, thereby preserving the integrity of the blood-brain barrier. Additionally, ELISA assays conducted using plasma samples from patients with varying NIHSS scores revealed statistically significant concentrations of PDGFRβ and MMP9. Furthermore, we developed a highly sensitive and specific quantitative detection method for PDGFRβ and MMP9 based on fluorescence sensor technology. This novel detector exhibits high sensitivity, repeatability, and stability, enabling precise dual detection. Thus, the results suggest the great potential of the detection of PDGFRβ and MMP9 for early diagnosis of IS and prognosis prediction of the disease.
研究领域:
神经科学
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医学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL PROLIFERATION
·
2023
·
IF 8.5
Yulan Chen,Xueyuan Bai,Jianwen Chen,Mengjie Huang,Quan Hong,Qing Ouyang,Xuefeng Sun,Yan Zhang,Jiaona Liu,Xu Wang,Lingling Wu,Xiangmei Chen
We aimed to investigate the role of renal pericyte pyruvate kinase M2 (PKM2) in the progression of acute kidney injury (AKI) to chronic kidney disease (CKD). The role of PKM2 in renal pericyte-myofibroblast transdifferentiation was investigated in an AKI-CKD mouse model. Platelet growth factor receptor beta (PDGFRβ)-iCreERT2; tdTomato mice were used for renal pericyte tracing. Western blotting and immunofluorescence staining were used to examine protein expression. An 5-ethynyl-2′-deoxyuridine assay was used to measure renal pericyte proliferation. A scratch cell migration assay was used to analyse cell migration. Seahorse experiments were used to examine glycolytic rates. Enzyme-linked immunoassay was used to measure pyruvate kinase enzymatic activity and lactate concentrations. The PKM2 nuclear translocation inhibitors Shikonin and TEPP-46 were used to alter pericyte transdifferentiation. In AKI-CKD, renal pericytes proliferated and transdifferentiated into myofibroblasts and PKM2 is highly expressed in renal pericytes. Shikonin and TEPP-46 inhibited pericyte proliferation, migration, and pericyte-myofibroblast transdifferentiation by reducing nuclear PKM2 entry. In the nucleus, PKM2 promoted downstream lactate dehydrogenase A (LDHA) and glucose transporter 1 (GLUT1) transcription, which are critical for glycolysis. Therefore, PKM2 regulates pericyte glycolytic and lactate production, which regulates renal pericyte-myofibroblast transdifferentiation. PKM2-regulated renal pericyte-myofibroblast transdifferentiation by regulating downstream LDHA and GLUT1 transcription and lactate production. Reducing nuclear PKM2 import can reduce renal pericytes-myofibroblasts transdifferentiation, providing new ideas for AKI-CKD treatment.
研究领域:
肾病学
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细胞生物学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
EXPERIMENTAL NEUROLOGY
·
2024
·
IF 4.6
Jing Qiu,Yi-Han Wang,Xiu-Ming Wang,Hui-Sheng Chen
The pericytes (PCs) surrounding capillaries are vital regulators of capillary constriction. Persistent PC contraction results in the increased capillary constriction, therefore leading to the impaired cerebral blood flow (CBF) recovery after reperfusion and worsening the clinical outcomes in stroke patients. However, the potential determinants of PC functions during ischemia/reperfusion are poorly understood. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit Delta (PIK3CD/PI3Kδ) is a crucial factor involved with neuronflammation during ischemic stroke. PI3Kδ has shown the expression in PCs, while its effect on PC functions has not been explored yet. In this study, a rodent ischemia/reperfusion model was established in C57BL/6 mice via transient middle cerebral artery occlusion and reperfusion (MCAO/R). The PI3Kδ expression in ischemic penumbra was remarkably upregulated following MCAO/R induction. PI3Kδ inhibitor CAL-101 improved the CBF recovery, ischemic brain injury, and suppressed capillary constriction in MCAO/R mice. Besides, the production of tumor necrosis factor alpha (TNF-α), an inducer for tissue injury, and the expression of transient receptor potential vanilloid type 2 (TRPV2), a channel protein permitting calcium (Ca 2+ ) uptake, were significantly reduced in ischemic penumbra after CAL-101 treatment. In vitro, oxygen-glucose deprivation and reoxygenation (OGD/R) enhanced the expression of PI3Kδ and TRPV2 in primary mouse PCs. CAL-101 suppressed the TNF-α-induced TRPV2 expression in OGD/R-treated PCs, thus inhibiting the Ca 2+ uptake and PC contraction. Collectively, this study suggests that PI3Kδ is a critical regulator of PC function during ischemic stroke.
研究领域:
神经科学
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
PLoS One
·
2024
·Vol. 19
·期 8
·e0308132
·
IF 2.9
Qingting Yu,Linyuan Zhang,Ting Xu,Jiapeng Shao,Falei Yuan,Zuisu Yang,Yuncheng Wu,Haiyan Lyu
To investigate the sex-dependent differentiation of Sox10 cells and their response to pathological conditions such as lipopolysaccharide (LPS) exposure or ischemia, we utilized Sox10 Cre-ER T2 , tdTomato mice. Tamoxifen administration induced the expression of red fluorescent protein (RFP) in these cells, facilitating their subsequent tracking and analysis after LPS injection and ischemia via immunofluorescence staining. Propidium iodide (PI) was injected to label necrotic cells following LPS administration. We found that the conversion of Sox10 cells to pericytes in female mice was significantly higher than in male mice, especially in those exposed to LPS. After LPS injection, the number of PI + necrotic cells were significantly greater in females than in males. Moreover, RFP + cells did not co-localize with glial fibrillary acidic protein (GFAP) or cluster of differentiation 11b (CD11b). Similarly, after brain ischemia, RFP + cells did not express cluster of differentiation 13 (CD13), neuronal nuclei (NeuN), GFAP, or ionised calcium binding adaptor molecule 1 (Iba-1). These findings indicate that the conversion of Sox10 cells to pericytes following LPS exposure is sex-dependent, with neither male nor female groups showing differentiation into other cell types after LPS exposure or under ischemic conditions. The differences in LPS-induced necrosis of pericytes between sexes may explain the variations in the conversion of Sox10 cells to pericytes in both sexes.
研究领域:
神经科学
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免疫学
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
EXPERIMENTAL EYE RESEARCH
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2022
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IF 3.77
Jun Chen,Yizhou Sun,Lei Chen,Yun Zhou
Diabetic retinopathy (DR) is a progressive vascular complication of diabetes mellitus (DM) and is related to retinal vascular abnormalities. NADH-Cytochrome B5 Reductase 2 (CBR2) has been implicated in angiogenesis , but the effect of CBR2 on angiogenesis and endothelial cell biological behavior in DR remains unclear. Here, we aimed to explore the effect of CBR2 on retinal vascular dysfunction under diabetic conditions. The histological analyses were performed to explore the effect of CBR2 on pathological change in streptozotocin (STZ)-induced diabetic rat retinas . The effect of CBR2 on endothelial cell function was explored by CCK-8, scratch wound, transwell, tube formation, and immunofluorescence assays in high glucose (HG)-stimulated human retinal microvascular endothelial cells (HRMECs). CBR2 expression was significantly downregulated in DM rat retinas and HG-stimulated HRMECs. Intravitreal injection of CBR2-expressing lentivirus under diabetic conditions reduced retinal angiogenesis, acellular capillary formation, and pericyte loss, along with decreased expression of hypoxia-inducible factor-1α (HIF-1α), cluster of differentiation 31 (CD31), and vascular endothelial growth factor A (VEGFA) in vivo . Moreover, CBR2 overexpression inhibited cell growth and tube formation and led to decreased expression of HIF-1α and VEGFA in HG-induced HRMECs. Interestingly, the repressive effects of CBR2 on cell proliferation , migration, and tube formation under HG conditions were strongly reversed when VEGFA was overexpressed. Overall, the key findings of our study suggested that CBR2 might alleviate retinal vascular dysfunction and abnormal endothelial proliferation during the process of DR by regulating VEGFA, providing a piece of potent evidence for DR therapy.
研究领域:
眼科学
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糖尿病
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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