EGb761 attenuates depressive-like behaviours induced by long-term light deprivation in C57BL/6J mice through inhibition of NF-κB-IL-6 signalling pathway

Abstract Background and Aims The mechanism of renal interstitial fibrosis occurs with kidney aging is unknown. Caloric restriction and caloric restriction mimetics (CRM) alleviate aging-related-fibrosis. The aim of this study is to investigate whether extracellular microvesicles (EVs) derived from senescent cells facilitate fibrosis development in aging kidney and the potential signalling pathway involved in the process. Method In this study, animal experiments included 3-mon-old ad libitum(YAL) rats, 24-mon-old ad libitum(OAL) rats and 24-mon-old caloric restriction(OCR) rats, which was given 70% of OAL’s for 8 months. Senescent cells were induced in proximal tubular epithelial cells(PTCs) by high glucose and further treated with resveratrol as CRM. The expression of miR-21, peroxisome proliferator-activated receptor(PPARα), hypoxia-inducible factor(HIF1α) in the kidney of rats and PTCs were examined. Epithelial to mesenchymal transition (EMT) and the related signalling pathway were detected by up- or down-regulation of miR-21, respectively. Results Long-term caloric restriction ameliorated senescent changes and aging-related fibrosis in aged ad libitum rat kidney. Caloric restriction blunted the increased expressions of miR-21 and HIF1α, the decreased expression of PPARα in renal tissue of old rats. High glucose induced PTCs senesence phenotype and EMT. miR-21 was detected in extracellular vesicles secreted by senescent PTC cells. CRMs resveratrol prevented EMT through downregulation of miR-21 in extracellular vesicles from the senescent PTC cells. Further, inhibiting miR-21 of donor senescent cells prevented the occurrence of EMT in recipient PTC cells. Finally, miR-21 induced EMT mainly through targeting PPARα protein and enhancing HIF1α expression. Conclusion This study demonstrated that miR-21-containing extracellular microvesicles derived from the senescent cells could facilitate tubular phenotype transition of neighbouring PTC cells via PPARα-HIF1α signalling pathway. Long-term caloric restriction and caloric restriction mimetics alleviate aging-related renal fibrosis through downregulation of miR-21 excretion.

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Reversible ultrastructural changes in the rhabdom of the locust eye are induced by long term light deprivation

Journal of Comparative Physiology A ◽

10.1007/bf00612567 ◽

1981 ◽

Vol 144 (3) ◽

pp. 357-365 ◽

Cited By ~ 9

Author(s):

Joseph W. Bloom ◽

Harold L. Atwood

Keyword(s):

Ultrastructural Changes ◽

Light Deprivation

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Is the Ras-MAPK signalling pathway necessary for long-term memory formation?

Trends in Neurosciences ◽

10.1016/s0166-2236(98)01306-x ◽

1999 ◽

Vol 22 (1) ◽

pp. 38-44 ◽

Cited By ~ 121

Author(s):

Paul C Orban ◽

Paul F Chapman ◽

Riccardo Brambilla

Keyword(s):

Memory Formation ◽

Signalling Pathway ◽

Long Term Memory ◽

Term Memory ◽

Mapk Signalling Pathway ◽

Mapk Signalling

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Oncogenic RAS Generates Cancer Stem Cells in p53-Deficient Fibroblasts Through SOX2 Induced By CDK1-Mediated Protein O-GlcNAcylation

10.21203/rs.3.rs-981157/v1 ◽

2021 ◽

Author(s):

Masahiro Shimizu ◽

Hiroshi Shibuya ◽

Nobuyuki Tanaka

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Gene Knockout ◽

Human Fibroblasts ◽

Signalling Pathway ◽

Oncogenic Ras ◽

Primary Mouse ◽

Underlying Mechanisms ◽

Tumour Initiation

Abstract Cancer stem cells (CSCs) have tumour initiation, self-renewal, and long-term tumour repopulation properties, and it is postulated that differentiated somatic cells can be reprogrammed to CSCs by oncogenic signals. We previously showed that oncogenic HRASV12 conferred tumour initiation capacity in tumour suppressor p53-deficient (p53−/−) primary mouse embryonic fibroblasts (MEFs) through transcription factor NF-κB-mediated enhancement of glucose uptake; however, the underlying mechanisms of RAS oncogene-induced CSC reprogramming have not been elucidated. Here, we found that the expression of the reprogramming factor SOX2 was induced by HRASV12 in p53−/− MEFs. Moreover, gene knockout studies revealed that SOX2 is an essential factor for the generation of CSCs by HRASV12 in mouse and human fibroblasts. We demonstrated that HRASV12-induced cyclin-dependent kinase 1 (CDK1) activity and subsequent enhancement of protein O-GlcNAcylation were required for SOX2 induction and CSC generation in these fibroblasts and cancer cell lines containing RAS mutations. Moreover, the CDK inhibitor dinaciclib and O-GlcNAcylation inhibitor OSMI1 reduced the number of CSCs derived from these cells. Taken together, our results reveal a signalling pathway and mechanism for CSC generation by oncogenic RAS and suggest the possibility that this signalling pathway is a therapeutic target for CSCs.

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