Requirement of Gαi1 and Gαi3 in interleukin-4-induced signaling, macrophage M2 polarization and allergic asthma response

Bai, Jinyu; Wang, Yongdong; Xue, Guanhua; Li, Ke-ran; Zheng, Yufan; Zhang, Zhiqing; Jiang, Qin; Liu, Yuan-yuan; Zhou, Xiaozhong; Cao, Cong

doi:10.7150/thno.56383

Cited by 36 publications

(70 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The cell line has previously been tested and authenticated by the Cell Bank of Shanghai Biological Institution. Wild-type (WT), Gαi1 and Gαi3 double knockout (DKO), Gαi1, Gαi2 or Gαi3 single knockout (SKO) mouse embryonic fibroblasts (MEFs), as well as WT and Gab1 KO MEFs, were cultivated as previously described 25 , 27 - 30 . Cells were starved in 0.5% FBS medium overnight plus 30 min warm PBS for signaling analyses.…”

Section: Methodsmentioning

confidence: 99%

Neuronal-driven glioma growth requires Gαi1 and Gαi3

Yin¹,

Liu²,

Chen³

et al. 2021

Theranostics

Self Cite

113

View full text Add to dashboard Cite

Neuroligin-3 (NLGN3) is necessary and sufficient to promote glioma cell growth. The recruitment of Gαi1/3 to the ligand-activated receptor tyrosine kinases (RTKs) is essential for mediating oncogenic signaling. Methods: Various genetic strategies were utilized to examine the requirement of Gαi1/3 in NLGN3-driven glioma cell growth. Results: NLGN3-induced Akt-mTORC1 and Erk activation was inhibited by decreasing Gαi1/3 expression. In contrast ectopic Gαi1/3 overexpression enhanced NLGN3-induced signaling. In glioma cells, NLGN3-induced cell growth, proliferation and migration were attenuated by Gαi1/3 depletion with shRNA, but facilitated with Gαi1/3 overexpression. Significantly, Gαi1/3 silencing inhibited orthotopic growth of patient-derived glioma xenografts in mouse brain, whereas forced Gαi1/3-overexpression in primary glioma xenografts significantly enhanced growth. The growth of brain-metastatic human lung cancer cells in mouse brain was largely inhibited with Gαi1/3 silencing. It was however expedited with ectopic Gαi1/3 overexpression. In human glioma Gαi3 upregulation was detected, correlating with poor prognosis. Conclusion: Gαi1/3 mediation of NLGN3-induced signaling is essential for neuronal-driven glioma growth .

show abstract

Section: Methodsmentioning

confidence: 99%

Neuronal-driven glioma growth requires Gαi1 and Gαi3

Yin¹,

Liu²,

Chen³

et al. 2021

Theranostics

Self Cite

113

View full text Add to dashboard Cite

show abstract

“…The detailed protocols for qPCR were previously described. 18 The qPCR was performed by the SYBR Premix Ex TaqTM kit under the ABI-7500 PCR system (Shanghai, China). 13 mRNA expression was quantified by 2 −ΔΔCt protocol with glyceraldehyde-3-phosphatedehydrogenase (GAPDH) as the internal control.…”

Section: Methodsmentioning

confidence: 99%

Injectable ROS-scavenging hydrogel with MSCs promoted the regeneration of damaged skeletal muscle

et al. 2021

View full text Add to dashboard Cite

Skeletal muscle injury is a common disease accompanied by inflammation, and its treatment still faces many challenges. The local inflammatory microenvironment can be modulated by a novel ROS-scavenging hydrogel (Gel) we constructed. And MSCs could differentiate into myoblasts and contribute to muscle tissue homeostasis and regeneration. Here, Gel loaded with mesenchymal stem cells (MSCs) (Gel@MSCs) was developed for repairing the injured skeletal muscle. Results showed that the Gel improved the survivability and enhanced the proliferation of MSCs (≈two-fold), and the Gel@MSCs inhibited the local inflammatory responses as it promoted polarization of M2 macrophages (increased from 5% to 17%), the mediator of the production of anti-inflammatory factors. Western blotting and qPCR revealed the Gel promoted the expression of proteins (≈two-fold) and genes (≈two to six-fold) related to myogenesis in MSCs. Histological assessment indicated that the Gel or MSCs promoted regeneration of skeletal muscle, and the efficacy was more significant at Gel@MSCs than MSCs alone. Finally, behavioral experiments confirmed that Gel@MSCs improved the motor function of injured mice. In short, the Gel@MSCs system we constructed presented a positive effect on reducing skeletal muscle damage and promoted skeletal muscle regeneration, which might be a novel treatment for such injuries.

show abstract

“…Next, a previously-described CRISPR/Cas9-Gαi3-KO-puro construct 15 , 16 was transduced to the Cas9-expressing pOS-1 primary cells. Thereafter, single stable pOS-1 cells with the Gαi3 KO construct, or the ko-Gαi3 cells, were established after Gαi3 KO screening, and Gαi3 mRNA and protein (Figure 4A ) depletion was detected.…”

Section: Resultsmentioning

confidence: 99%

“…Our group has identified an essential role of Gαi proteins in transducing signals for multiple RTKs [14][15][16][17][18][19][20]. We found that EGFR-induced Akt-mTOR activation was abolished after Gαi1/3 double knockout (DKO) or silencing [20].…”

Section: Introductionmentioning

confidence: 99%

Identification of Gαi3 as a promising target for osteosarcoma treatment

Bian¹,

Shan²,

Zhu³

et al. 2022

Int. J. Biol. Sci.

Self Cite

View full text Add to dashboard Cite

Sustained activation of multiple receptor tyrosine kinases (RTKs) simultaneously is vital for tumorigenesis and progression of osteosarcoma (OS). Gαi proteins recruitment to various RTKs mediates downstream oncogenic signaling activation. The expression, functions and underlying mechanisms of Gαi3 in human OS were examined. Expression of Gαi3 is robustly elevated in human OS tissues and is correlated with a poor overall survival. In patient-derived primary OS cells and immortalized lines (MG63 and U2OS), Gαi3 depletion, by shRNA and CRISPR/Cas9 strategies, robustly suppressed cell viability, proliferation and migration, while provoking G1-S arrest and apoptosis activation. Conversely, Gαi3 overexpressing ectopically can accelerate proliferation and migration of OS cells. In OS cells, Gαi3 immunoprecipitated with VEGFR2, FGFR, PGDFR and EGFR, mediating downstream cascade transduction. Akt-mTOR activation in primary OS cells was potently inhibited by Gαi3 shRNA, knockout or dominant negative mutation, but augmented after Gαi3 overexpression. In vivo studies showed that Gαi3 shRNA AAV (adeno-associated viruses) intratumoral injection largely inhibited the growth of subcutaneous xenografts of primary OS cells. Moreover, the growth of the Gαi3-knockout primary OS xenografts was much slower than that of OS xenografts with empty vector. In Gαi3-depleted OS xenografts tissues, Gαi3 downregulation and Akt-mTOR inactivation were detected. Taken together, overexpressed Gαi3 mediates RTK-Akt signaling to drive OS progression.

show abstract

Requirement of Gαi1 and Gαi3 in interleukin-4-induced signaling, macrophage M2 polarization and allergic asthma response

Cited by 36 publications

References 56 publications

Neuronal-driven glioma growth requires Gαi1 and Gαi3

Neuronal-driven glioma growth requires Gαi1 and Gαi3

Injectable ROS-scavenging hydrogel with MSCs promoted the regeneration of damaged skeletal muscle

Identification of Gαi3 as a promising target for osteosarcoma treatment

Contact Info

Product

Resources

About