αB-crystallin regulation of angiogenesis by modulation of VEGF

Kase, Satoru; He, Shikun; Sonoda, Shozo; Kitamura, M.; Spee, Christine; Wawrousek, Eric F.; Ryan, Stephen J.; Kannan, Ram; Hinton, David R.

doi:10.1182/blood-2009-01-197095

Cited by 145 publications

(176 citation statements)

References 41 publications

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“…Fibrosis continues to increase for up to 35 days after laser ( Figure 1A). As shown previously, 22 CNV volume at day 7 after laser was reduced in aB-crystallin À/À mice compared with the WT mice. At days 21 and 35 after laser, no significant difference was seen in CNV volume between WT and aB-crystallin À/À mice.…”

Section: Attenuation Of Subretinal Fibrosis In Ab-crystallin à/à Micesupporting

confidence: 85%

“…25 Laser-Induced CNV CNVs were generated as described previously. 22 Briefly, laser photocoagulation (532 nm, 150 mW, 50 milliseconds, 75 mm) was applied to each fundus using a coverslip as a contact lens on day 0. We made four laser spots per eye for immunohistochemistry and 20 laser spots for extracting protein for enzyme-linked immunosorbent assay (ELISA) analysis.…”

Section: Rpe Cell Culturementioning

confidence: 99%

“…Realtime quantitative RT-PCR was performed, as described previously. 22 To eliminate contamination of genomic or plasmid DNA, we pretreated total RNA with DNase (Life Technologies) before proceeding to reverse transcription. The primer sequences are shown in Table 3.…”

Section: Rna Isolation and Real-time Quantitative Rt-pcrmentioning

confidence: 99%

“…Immunofluorescence staining for the sections was performed as described previously. 22 Pan-cytokeratin-positive cells or cells positive for a-SMA or E-cadherin were calculated as the number of the immunoreactive cells per mm 2 of CNV area at day 35 after laser, according to the method previously reported. 7 The average percentage of the cells immunoreactive for a-SMA or E-cadherin in pan-cytokeratin-positive cells was calculated from four eyes.…”

Section: Immunohistochemistry and Immunofluorescence Stainingmentioning

confidence: 99%

“…In addition, we previously demonstrated that aB-crystallin plays a regulatory role by functioning as a chaperone for VEGF in ocular angiogenesis and may play a part in CNV formation in nAMD. 22 However, the involvement of aB-crystallin in subretinal fibrosis in nAMD has not been studied.…”

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confidence: 99%

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αB-Crystallin Regulates Subretinal Fibrosis by Modulation of Epithelial-Mesenchymal Transition

Ishikawa

Sreekumar

Spee

et al. 2016

The American Journal of Pathology

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Subretinal fibrosis is an end stage of neovascular age-related macular degeneration, characterized by fibrous membrane formation after choroidal neovascularization. An initial step of the pathogenesis is an epithelial-mesenchymal transition (EMT) of retinal pigment epithelium cells. aB-crystallin plays multiple roles in age-related macular degeneration, including cytoprotection and angiogenesis. However, the role of aB-crystallin in subretinal EMT and fibrosis is unknown. Herein, we showed attenuation of subretinal fibrosis after regression of laser-induced choroidal neovascularization and a decrease in mesenchymal retinal pigment epithelium cells in aB-crystallin knockout mice compared with wild-type mice. aB-crystallin was prominently expressed in subretinal fibrotic lesions in mice. In vitro, overexpression of aB-crystallin induced EMT, whereas suppression of aB-crystallin induced a mesenchymal-epithelial transition. Transforming growth factor-b2einduced EMT was further enhanced by overexpression of aB-crystallin but was inhibited by suppression of aB-crystallin. Silencing of aB-crystallin inhibited multiple fibrotic processes, including cell proliferation, migration, and fibronectin production. Bone morphogenetic protein 4 upregulated aB-crystallin, and its EMT induction was inhibited by knockdown of aB-crystallin. Furthermore, inhibition of aB-crystallin enhanced monotetraubiquitination of SMAD4, which can impair its nuclear localization. Overexpression of aB-crystallin enhanced nuclear translocation and accumulation of SMAD4 and SMAD5. Thus, aB-crystallin is an important regulator of EMT, acting as a molecular chaperone for SMAD4 and as its potential therapeutic target for preventing subretinal fibrosis development in neovascular age-related macular degeneration. (Am J Pathol 2016, 186: 859e873; http:// dx

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Section: Attenuation Of Subretinal Fibrosis In Ab-crystallin à/à Micesupporting

confidence: 85%

Section: Rpe Cell Culturementioning

confidence: 99%

Section: Rna Isolation and Real-time Quantitative Rt-pcrmentioning

confidence: 99%

Section: Immunohistochemistry and Immunofluorescence Stainingmentioning

confidence: 99%

mentioning

confidence: 99%

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αB-Crystallin Regulates Subretinal Fibrosis by Modulation of Epithelial-Mesenchymal Transition

Ishikawa

Sreekumar

Spee

et al. 2016

The American Journal of Pathology

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Thermal denaturation and aggregation of apoform of glycogen phosphorylase b. Effect of crowding agents and chaperones

et al. 2014

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The effect of protein and chemical chaperones and crowders on thermal stability and aggregation of apoform of rabbit muscle glycogen phosphorylase b (apoPhb) has been studied at 37°C. Proline suppressed heat-induced loss in ability of apoPhb to reconstitution at 37°C, whereas α-crystallin did not reveal a protective action. To compare the antiaggregation activity of intact and crosslinked α-crystallins, an adsorption capacity (AC) of a protein chaperone with respect to a target protein was estimated. This parameter is a measure of the antiaggregation activity. Crosslinking of α-crystallin results in 11-fold decrease in the initial AC. The nonlinear character of the relative initial rate of apoPhb aggregation versus the [intact α-crystallin]/[apoPhb] ratio plot is indicative of the decrease in the AC of α-crystallin with increasing the [α-crystallin]/[apoPhb] ratio and can be interpreted as an evidence for dynamic chaperone structure and polydispersity of α-crystallin-target protein complexes. As for chemical chaperones, a semisaturation concentration of the latter was used as a characteristic of the antiaggregation activity. A decrease in the semisaturation concentration for proline was observed in the presence of the crowders (polyethylene glycol and Ficoll-70).

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TMT‐based proteomics analysis of the effects of Qianjinweijing Tang on lung cancer

Huo

Song

Tan

et al. 2021

Biomedical Chromatography

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Qianjinweijing Tang (QJWJ) is a classic traditional Chinese formula that is often used in the treatment of treat lung cancer (LC). However, the underlying cellular mechanisms of the anticancer effects of QJWJ remain unclear. Cell viability was determined by MTS assay and levels of apoptosis measured by flow cytometry.Animal experiments were conducted to determine the effects of QJWJ on tumor growth in vivo. We used a proteomics approach to study the effects of QJWJ on LC cells and applied bioinformatics analysis to identify differentially expressed proteins that were validated by western blotting. QJWJ inhibited the proliferation of LC cells and induced apoptosis. The tumor growth delay effects of QJWJ were confirmed in vivo. We identified 104 differentially expressed proteins following QJWJ treatments of which 45 proteins were upregulated and 59 were downregulated. The levels of differentially expressed proteins were validated by western blotting. Our study indicated that QJWJ has anticancer effects in vivo and in vitro and that these effects are mediated by modulating the expression of tumor-related proteins.

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αB-crystallin regulation of angiogenesis by modulation of VEGF

Cited by 145 publications

References 41 publications

αB-Crystallin Regulates Subretinal Fibrosis by Modulation of Epithelial-Mesenchymal Transition

αB-Crystallin Regulates Subretinal Fibrosis by Modulation of Epithelial-Mesenchymal Transition

Thermal denaturation and aggregation of apoform of glycogen phosphorylase b. Effect of crowding agents and chaperones

TMT‐based proteomics analysis of the effects of Qianjinweijing Tang on lung cancer

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