EMBO JOURNAL
·
2020
·Vol. 39
·期 5
·e101679
·
IF 9.889
Jun Wu,Wen-Jia Tian,Yang Liu,Huanhuan J Wang,Jiangli Zheng,Xin Wang,Han Pan,Ji Li,Junyu Luo,Xuerui Yang,Lester F Lau,H Troy Ghashghaei,Qin Shen
Adult neural stem cells (NSCs) reside in specialized niches, which hold a balanced number of NSCs, their progeny, and other cells. How niche capacity is regulated to contain a specific number of NSCs remains unclear. Here, we show that ependyma-derived matricellular protein CCN1 (cellular communication network factor 1) negatively regulates niche capacity and NSC number in the adult ventricular–subventricular zone (V-SVZ). Adult ependyma-specific deletion of Ccn1 transiently enhanced NSC proliferation and reduced neuronal differentiation in mice, increasing the numbers of NSCs and NSC units. Although proliferation of NSCs and neurogenesis seen in Ccn1 knockout mice eventually returned to normal, the expanded NSC pool was maintained in the V-SVZ until old age. Inhibition of EGFR signaling prevented expansion of the NSC population observed in CCN1 deficient mice. Thus, ependyma-derived CCN1 restricts NSC expansion in the adult brain to maintain the proper niche capacity of the V-SVZ.
研究领域:
神经科学
·
干细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
·
2025
·Vol. 63
·期 1
·229
·
IF 4.3
Zhang Zhiyang,Xu Nixi,Tao Zean,Liang Yun,Jin Lixia,Li Zhuoxuan,Cao Yuanwu,Jiang Chang,Chen Zixian
Spinal cord injury (SCI) often results in permanent functional loss due to the complexity of the post-SCI microenvironment, but the composition and functional dynamics of the post-SCI microenvironment remain poorly understood. We applied spatial metabolomics to detect metabolites within the spinal cord of SCI rats, revealing the existence of a high-uric acid (hUA) microenvironment. Subsequently, we utilized Bulk-RNA sequencing and single-cell RNA sequencing (scRNA-seq) analysis, identified elevated expression of Cellular communication network factor 1 (Ccn1) and alterations in purine metabolic patterns. To investigate the role of Ccn1 within this hUA microenvironment, PC12 cell line and Sprague–Dawley (SD) rats were used. In vitro , 4 groups were designed: Control ( n = 6), UA (PC12 cells treated with 200 μM UA for 24 h) ( n = 6), siCcn1 ( Ccn1 knockdown using small interfering RNA) ( n = 6), and siCcn1 + UA ( n = 6). In vivo groups: SCI (spinal cord injury only) ( n = 6), hUA (induced hUA microenvironment by gavage with oxonic acid potassium salt 750 mg/kg and and ethambutol 250 mg/kg) ( n = 6), AAV ( Ccn1 knockdown via adeno-associated virus) ( n = 6), and AAV + hUA ( n = 6). Results showed that UA significantly reduced cellular aerobic respiration levels (Control vs UA: 62.87 ± 16.76 vs 17.09 ± 4.91 pmol/min, P < 0.01) and induced pyroptosis, Ccn1 knockdown significantly improved aerobic respiration ( siCcn1 + UA vs UA: 46.45 ± 12.54 vs 17.09 ± 4.91 pmol/min, P < 0.05) and reduced the level of pyroptosis. Total cellular ATP levels, the NAD⁺/NADH ratio, and proliferation capacity were also assessed. In vivo , Ccn1 knockdown significantly increased the Basso, Beattie, and Bresnahan (BBB) locomotor scores of animals on the 7 days post-injury ( AAV + hUA vs hUA: 3.33 ± 0.52 vs 2.00 ± 0.63, P < 0.05) and reduced neuronal pyroptosis. The hUA microenvironment upregulated Ccn1 expression, suppressed aerobic respiration, induced pyroptosis, and disrupted purine metabolism, Ccn1 knockdown reversed these biological processes, suggesting its potential as a therapeutic target for SCI.
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产品关联
DOI
PubMed
高影响因子
Journal of Cosmetic Dermatology
·
2026
·Vol. 25
·期 7
·e71010
·
IF 3.5
Liying Kang,Yanhong Liu,Yuchen Xin,Lin Geng,Shaochun Cai,Jianfang Luo,Shaojie Gu,Shuangyan Wang,Zhiting Zhang,Yan Huang,Guixuan Zhou,Li Ye,Dongcui Li,Naisheng Jiang
Background Cellular Communication Network Factor 1 (CCN1) has been identified as a key regulator of oxidative stress‐induced skin aging and sensitivity. Ashwagandha root extract (ARE) is a promising candidate for modulating CCN1‐associated pathways. Aims To investigate whether ARE can mitigate sensitive‐skin aging by modulating CCN1 expression and its downstream effects, and to evaluate the clinical efficacy and tolerability of an ARE‐containing formulation in individuals with sensitive skin. Methods Human foreskin fibroblasts (HFF‐1) exposed to hydrogen peroxide (H 2 O 2 ) were assessed for viability using the Cell Counting Kit‐8 (CCK‐8) assay, and for CCN1, integrin α 6 β 1 , MMP‐1, COL‐1, IL‐6, and IL‐1β expression using enzyme‐linked immunosorbent assay (ELISA). A 28‐day open‐label clinical study was performed in 31 Chinese women with sensitive skin to evaluate changes in skin hydration, elasticity, firmness, wrinkle severity, and facial contour. Results H 2 O 2 exposure significantly decreased fibroblast viability and upregulated CCN1 expression. Treatment with ARE dose‐dependently restored cell viability, suppressed the expression of CCN1, integrin α 6 β 1 , MMP‐1, IL‐6, and IL‐1β, and promoted COL‐1 synthesis. Clinical evaluation demonstrated that 28 days of ARE‐containing cream application significantly improved skin hydration (+49.0%) and elasticity (+27.2%), improved skin firmness, as evidenced by a 32.4% reduction in the F4 parameter compared with baseline ( p < 0.001), and reduced wrinkle depth and facial sagging. Conclusion ARE can alleviate oxidative stress‐induced skin aging at least in part by downregulating CCN1 and its downstream inflammatory mediators and by inhibiting matrix‐metalloproteinase‐mediated extracellular matrix (ECM) degradation. The combined biological and clinical evidence supports ARE as a promising and well‐tolerated active ingredient for improving signs of skin aging in individuals with sensitive skin.
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产品关联
DOI
高影响因子
Clinics and Research in Hepatology and Gastroenterology
·
2021
·
IF 2.947
Huanqiu Liu,Ji Li,Chengwei Jiang,Tong Yuan,Haichun Ma
Objective Hepatic ischemia/reperfusion injury (IRI) is an unsettled and intractable conundrum in clinical treatment after liver transplantation and resection. Cellular communication network factor 1 (CCN1) is upregulated in liver IRI and may play a key role in this process. The objective of this study is to investigate the regulatory mechanism of CCN1 in liver IRI, which may provide new insight into liver IRI clinical treatment. Methods The hepatic ischemia/reperfusion model was established in male C57BL/6 mice by occlusion of vessels in the liver followed by reperfusion. The mice were transfected with two small interfering RNAs (siRNAs) against CCN1 for CCN1 knockdown. The hypoxia/reoxygenation (HR) model was established in vitro using mouse hepatic cells followed by transfection with a siRNA and treatment with an ERK activator TPA to confirm the effects of CCN1 on the MEK/ERK pathway in liver IRI. Results In hepatic IRI, CCN1 was upregulated and its knockdown reduced alanine aminotransferase and aspartate transaminase levels, myeloperoxidase activity, and the levels of IL-6 and TNF-α. CCN1 downregulation alleviated inflammatory cell infiltration and apoptosis in the liver. The expressions of cleaved caspase-9, cleaved caspase-3, Bax, and CHOP were decreased with an increased Bcl-2 level after CCN1 knockdown. The phosphorylation and activation of proteins in ER stress and MEK/ERK pathway were inhibited by CCN1 knockdown. In vitro , the levels of proinflammatory cytokines, apoptosis-inducing proteins, and proteins in ER stress and MEK/ERK pathway, which were decreased by CCN1 knockdown in HR, were restored by TPA, confirming that the activation of ERK aggravated cell apoptosis after reoxygenation. Conclusion Overall, CCN1 knockdown may suppress the inflammation, apoptosis during hepatic IRI by reducing the MEK/ERK pathway activation, which may be a breakthrough point in clinical alleviation of hepatic IRI caused by liver transplantation and resection.
研究领域:
肝病学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
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