scholarly journals Proline-rich tyrosine kinase 2 via enhancing signal transducer and activator of transcription 3-dependent cJun expression mediates retinal neovascularization

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Raj Kumar ◽  
Nikhlesh K. Singh ◽  
Gadiparthi N. Rao
Keyword(s):  
Tyrosine Kinase ◽  
Retinal Neovascularization ◽  
Signal Transducer ◽  
Tyrosine Kinase 2 ◽  
Transcription 3

Periplaneta Americana Extract May Attenuate Renal Fibrosis through Inhibiting Janus Tyrosine Kinase 2/Signal Transducer and Activator of Transcription 3 Pathway

Pharmacology ◽  
2018 ◽  
Vol 102 (1-2) ◽  
pp. 1-8 ◽  
Author(s):  
Jingsong Liu ◽  
Lin Zhou ◽  
Liyu He ◽  
Ying Zhong ◽  
Xiaobai Zhang ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Renal Fibrosis ◽  
Periplaneta Americana ◽  
Smooth Muscle Actin ◽  
Signal Transducer ◽  
Alpha Smooth Muscle Actin ◽  
Tyrosine Kinase 2 ◽  
Janus Tyrosine Kinase 2 ◽  
Transcription 3

Background: Periplaneta americana is one of the ancient insect groups with the strongest vitality. Periplaneta americana extract (PAE) has been explored as an alternative remedy for many diseases. Although much progress has been made in the study about PAE, the role of the drug in renal disease is rarely reported, especially in renal fibrosis. This study was designed to evaluate the renoprotective effect of PAE treatment to renal fibrosis. Method: An in vivo, unilateral ureteral obstruction (UUO) mouse model was built. Then the mice were treated with PAE (100 mg/kg body weight) once daily by oral gavage, again starting on the day of UUO and continued for 1 week. At the end of 1 week, the mice were sacrificed; kidney samples were collected for further analysis. In vitro, Boston University mouse proximal tubular cells were plated in 35-mm dishes at a density of 0.3 * 106 cells/dish. Then the cells were treated with 5-ng/mL TGF-β1 in serum-free DMEM medium for an indicated length of time. The experimental groups were pretreated with the indicated concentrations of PAE (0.3125 mg/mL). The cells were further cultured for 24 h, and then cells were monitored morphologically or collected for biochemical analyses. Results: Both in vivo and vitro PAE inhibits the expression of FN and alpha-smooth muscle actin and suppresses renal fibrosis. Importantly, PAE protects against renal fibrosis by inhibiting Janus tyrosine kinase 2 (JAK)/signal transducer and activator of transcription 3 (STAT) tyrosine phosphorylation. Conclusion: PAE attenuates renal fibrosis through the suppression of the JAK2/STAT3 pathway.

scholarly journals Hyaloid Vasculature as a Major Source of STAT3 + (Signal Transducer and Activator of Transcription 3) Myeloid Cells for Pathogenic Retinal Neovascularization in Oxygen-Induced Retinopathy

2020 ◽  
Vol 40 (12) ◽  
Author(s):  
Jose R. Hombrebueno ◽  
Aisling Lynch ◽  
Eimear M. Byrne ◽  
Gideon Obasanmi ◽  
Adrien Kissenpfennig ◽  
...  
Keyword(s):  
Myeloid Cells ◽  
Retinal Neovascularization ◽  
Cytokine Signaling ◽  
Strongly Correlated ◽  
Signal Transducer ◽  
Oxygen Induced Retinopathy ◽  
Retinal Angiogenesis ◽  
Ischemic Retina ◽  
Transcription 3 ◽  
Hyaloid Vasculature

Objective: Myeloid cells are critically involved in inflammation-induced angiogenesis, although their pathogenic role in the ischemic retina remains controversial. We hypothesize that myeloid cells contribute to pathogenic neovascularization in retinopathy of prematurity through STAT3 (signal transducer and activator of transcription 3) activation. Approach and Results: Using the mouse model of oxygen-induced retinopathy, we show that myeloid cells (CD45 + IsolectinB4 [IB4] + ) and particularly M2-type macrophages (CD45 + Arg1 + ), comprise a major source of STAT3 activation (pSTAT3) in the immature ischemic retina. Most of the pSTAT3-expressing myeloid cells concentrated at the hyaloid vasculature and their numbers were strongly correlated with the severity of pathogenic neovascular tuft formation. Pharmacological inhibition of STAT3 reduced the load of IB4 + cells in the hyaloid vasculature and significantly reduced the formation of pathogenic neovascular tufts during oxygen-induced retinopathy, leading to improved long-term visual outcomes (ie, increased retinal thickness and scotopic b-wave electroretinogram responses). Genetic deletion of SOCS3 (suppressor of cytokine signaling 3), an endogenous inhibitor of STAT3, in myeloid cells, enhanced pathological and physiological neovascularization in oxygen-induced retinopathy, indicating that myeloid-STAT3 signaling is crucial for retinal angiogenesis. Conclusions: Circulating myeloid cells may migrate to the immature ischemic retina through the hyaloid vasculature and contribute to retinal neovascularization via activation of STAT3. Understanding how STAT3 modulates myeloid cells for vascular repair/pathology may provide novel therapeutic options in pathogenic angiogenesis.

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