Young bone marrow Sca‐1 cells protect aged retina from ischaemia‐reperfusion injury through activation of <scp>FGF</scp>2

Shao, Zhengbo; Wu, Jie; Du, Guoqing; Song, Hui‐Fang; Li, Shuhong; He, Sheng; Li, Jiao; Wu, Jun; Weisel, Richard D.; Yuan, Huiping; Li, Ren‐Ke

doi:10.1111/jcmm.13905

Cited by 15 publications

(22 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ADAMTS9 exhibited promoter hypermethylation and its downregulation is associated with decreased cell proliferation and increased apoptosis. Interestingly, these findings were confirmed by a recent study 20 .…”

Section: Resultssupporting

confidence: 81%

See 1 more Smart Citation

Interpreting pathways to discover cancer driver genes with Moonlight

et al. 2020

View full text Add to dashboard Cite

Cancer driver gene alterations influence cancer development, occurring in oncogenes, tumor suppressors, and dual role genes. Discovering dual role cancer genes is difficult because of their elusive context-dependent behavior. We define oncogenic mediators as genes controlling biological processes. With them, we classify cancer driver genes, unveiling their roles in cancer mechanisms. To this end, we present Moonlight, a tool that incorporates multiple -omics data to identify critical cancer driver genes. With Moonlight, we analyze 8000+ tumor samples from 18 cancer types, discovering 3310 oncogenic mediators, 151 having dual roles. By incorporating additional data (amplification, mutation, DNA methylation, chromatin accessibility), we reveal 1000+ cancer driver genes, corroborating known molecular mechanisms. Additionally, we confirm critical cancer driver genes by analysing cell-line datasets. We discover inactivation of tumor suppressors in intron regions and that tissue type and subtype indicate dual role status. These findings help explain tumor heterogeneity and could guide therapeutic decisions.

show abstract

Section: Resultssupporting

confidence: 81%

“…These patterns (Fig. 2b) were (i) increased proliferation and decreased apoptosis (e.g., CDC20 17 , TIMELESS 18 , and CDC6 19 ), and (ii) decreased proliferation and increased apoptosis (e.g., ADAMTS9 20 , DLL4 21 , and SOX7 22 ). We supported our findings by literature searches (Fig.…”

Section: Resultsmentioning

confidence: 99%

Interpreting pathways to discover cancer driver genes with Moonlight

et al. 2020

View full text Add to dashboard Cite

show abstract

“…F-VEP and light/dark transition tests were used to detect the visual function of mice as previously described 43 . In brief, the active electrode, reference electrode and ground electrode were inserted under the skin of the occiput, mandible and upper limb of mice to perform f-VEP.…”

Section: Methodsmentioning

confidence: 99%

The E50K optineurin mutation impacts autophagy-mediated degradation of TDP-43 and leads to RGC apoptosis in vivo and in vitro

et al. 2021

Self Cite

View full text Add to dashboard Cite

The glaucoma-associated E50K mutation in optineurin (OPTN) is known to affect autophagy and cause the apoptosis of retinal ganglion cells (RGCs), but the pathogenic mechanism remains unclear. In this study, we investigated whether the OPTN (E50K) mutation caused TDP-43 aggregation by disrupting autophagy in vivo and in vitro. OPTN (E50K) mutant mice were generated and analysed for genotype and phenotype. Adeno-associated virus type 2 vectors containing either GFP only, GFP-tagged wild-type OPTN or GFP-tagged E50K-mutated OPTN were used to transfect R28 cells. Loss of RGCs decreased retinal thickness and visual impairment were observed in OPTN (E50K) mice compared with WT mice. Moreover, overexpression of E50K OPTN induced R28 cell apoptosis. Increased p62/SQSTM1 and LC3-II levels indicated that autophagic flux was inhibited and contributed to TDP-43 aggregation in vivo and in vitro. We found that rapamycin effectively reduced the aggregation of TDP-43 in OPTN (E50K) mice and decreased the protein levels of p62/SQSTM1 and the autophagic marker LC3-II. Moreover, rapamycin increased the RGC number and visual function of E50K mice. In addition, we also observed increased cytoplasmic TDP-43 in the spinal cord and motor dysfunction in 24-month-old OPTN (E50K) mice, indicating that TDP-43 accumulation may be the common pathological mechanism of glaucoma and amyotrophic lateral sclerosis (ALS). In conclusion, the disruption of autophagy by OPTN (E50K) affected the degradation of TDP-43 and may play an important role in OPTN (E50K)-mediated glaucomatous retinal neurodegeneration.

show abstract

“…Before mice were sacri ced for the proteomics analysis, several measuring procedures were conducted to verify their visual conditions [10]. Brie y, IOP was monitored using an Icare Tonometer (Finland) (Supplemental Fig.…”

Section: Animal Models and Their Visual Conditionsmentioning

confidence: 99%

Proteomic Comparison of Aged and OPTN E50K Retina in the Development of Normal Tension Glaucoma

Liu

Wang

Shao

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Progressive degeneration of retinal ganglion cells (RGCs) is a major characteristic of glaucoma, whose underlying mechanisms are still largely unknown. An E50K mutation in the Optineurin (OPTN) gene is a leading cause of normal tension glaucoma (NTG), directly affecting RGCs without high intraocular pressure and causing severe glaucomatous symptoms in clinical settings. A systematic analysis of the NTG mouse model is crucial for better understanding of the underlying pathological mechanisms for glaucoma.Methods: To elucidate proteomic and biochemical pathway alterations during NTG development, we established an OPTN E50K mutant mouse model through CRISPR/Cas9. Retinal proteins from resulting mice exhibiting glaucomatous phenotypes were subject to tandem mass tag-labelled quantitative proteomics. Retinal proteomes were analyzed through bioinformatics methods to characterize the molecular and functional signatures of NTG. Results: We identified 6364 quantitative proteins in our proteomic analysis. Bioinformatics analysis revealed that OPTN E50K mice experienced protein synthesis dysregulation, age-dependent energy defects and autophagy-lysosome pathway dysfunction. Certain biological features, including amyloid deposition, RNA splicing, microglia activation and reduction of crystallin production, were similar to Alzheimer’s Disease (AD). Conclusions: Our study is the first to describe proteomic and biochemical pathway alterations in NTG pathogenesis during disease advancement. Several proteomic signatures overlapped with retinal changes found in the AD mice model, suggesting the presence of common mechanisms between age-related degenerative disorders, as well as prospective new targets for diagnostic and therapeutic strategies.

show abstract

Young bone marrow Sca‐1 cells protect aged retina from ischaemia‐reperfusion injury through activation of FGF2

Cited by 15 publications

References 49 publications

Interpreting pathways to discover cancer driver genes with Moonlight

Interpreting pathways to discover cancer driver genes with Moonlight

The E50K optineurin mutation impacts autophagy-mediated degradation of TDP-43 and leads to RGC apoptosis in vivo and in vitro

Proteomic Comparison of Aged and OPTN E50K Retina in the Development of Normal Tension Glaucoma

Contact Info

Product

Resources

About