GSTA3 regulates TGF-<b>β</b>1-induced renal interstitial fibrosis in NRK-52E cells as a component of the PI3K–Keap1/Nrf2 pathway

Xiao, Yun; Zhang, Zhiwei; Fu, Yingyu; Shan, Huizhi; Cui, Sini; Wu, Jun

doi:10.1177/0300060519876796

Cited by 9 publications

(5 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Transmembrane 26 (Tmem26) is a surface marker protein of beige adipocytes, and M2 macrophage activation contributes to beige fat development [ 27 , 28 ]. Glutathione S-transferase alpha 3 (Gsta3) is a member of the GST family and is a detoxification enzyme that protects against oxidative stress [ 29 ]. Increased oxidative stress promotes osteoclastic bone remodeling and decreased bone loss [ 30 ].…”

Section: Resultsmentioning

confidence: 99%

Identification of Novel Genes for Cell Fusion during Osteoclast Formation

Cho

Cheon²,

Ding³

et al. 2022

IJMS

View full text Add to dashboard Cite

Osteoclasts are derived from hematopoietic stem cells. Monocyte preosteoclasts obtain resorbing activity via cell–cell fusion to generate multinucleated cells. However, the mechanisms and molecules involved in the fusion process are poorly understood. In this study, we performed RNA sequencing with single nucleated cells (SNCs) and multinucleated cells (MNCs) to identify the fusion-specific genes. The SNCs and MNCs were isolated under the same conditions during osteoclastogenesis with the receptor activator of nuclear factor-κB ligand (RANKL) administration. Based on this analysis, the expression of seven genes was found to be significantly increased in MNCs but decreased in SNCs, compared to that in bone marrow-derived macrophages (BMMs). We then generated knockout macrophage cell lines using a CRISPR-Cas9 genome-editing tool to examine their function during osteoclastogenesis. Calcrl-, Marco-, or Ube3a-deficient cells could not develop multinucleated giant osteoclasts upon RANKL stimulation. However, Tmem26-deficient cells fused more efficiently than control cells. Our findings demonstrate that Calcrl, Marco, and Ube3a are novel determinants of osteoclastogenesis, especially with respect to cell fusion, and highlight potential targets for osteoporosis therapy.

show abstract

Section: Resultsmentioning

confidence: 99%

Identification of Novel Genes for Cell Fusion during Osteoclast Formation

Cho

Cheon²,

Ding³

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…GSTA3, which is one of the most important members of the glutathione transferase family and is involved in the detoxification and cellular defense ( Hayes et al, 2005 ), it was reported to attenuate renal interstitial fibrosis in vivo and in vitro by inhibiting the activity of the TGF-β1 signaling pathway ( Xiao et al, 2016 ; Xiao et al, 2019 ) and inhibited liver fibrosis through the suppression of the MAPK and GSK-3β signaling pathways ( Chen et al, 2019 ), suggesting that GSTA3 is an effective anti-fibrosis target. S100A9 was not only identified as a marker for idiopathic pulmonary fibrosis ( Hara et al, 2012 ; Yamashita et al, 2021 ), but also aggravated dermal fibrosis induced by bleomycin in mice via activation of ERK1/2 MAPK and NF-κB pathways ( Xu et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Yi-Shen-Hua-Shi Granule Alleviates Adriamycin-Induced Glomerular Fibrosis by Suppressing the BMP2/Smad Signaling Pathway

Tan

Si²,

Yu³

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Focal segmental glomerulosclerosis (FSGS) is a common clinical condition with manifestations of nephrotic syndrome and fibrosis of the glomeruli and interstitium. Yi-Shen-Hua-Shi (YSHS) granule has been shown to have a good effect in alleviating nephrotic syndrome (NS) in clinical and in animal models of FSGS, but whether it can alleviate renal fibrosis in FSGS and its mechanism and targets are not clear. In this study, we explored the anti-fibrotic effect and the targets of the YSHS granule in an adriamycin (ADR)-induced FSGS model and found that the YSHS granule significantly improved the renal function of ADR-induced FSGS model mice and also significantly reduced the deposition of collagen fibers and the expression of mesenchymal cell markers FN, vimentin, and α-SMA in the glomeruli of ADR-induced FSGS mice, suggesting that the YSHS granule inhibited the fibrosis of sclerotic glomeruli. Subsequently, a network pharmacology-based approach was used to identify the potential targets of the YSHS granule for the alleviation of glomerulosclerosis in FSGS, and the results showed that the YSHS granule down-regulated the expressions of BMP2, GSTA1, GATS3, BST1, and S100A9 and up-regulated the expressions of TTR and GATM in ADR-induced FSGS model mice. We also proved that the YSHS granule inhibited the fibrosis in the glomeruli of ADR-induced FSGS model mice through the suppression of the BMP2/Smad signaling pathway.

show abstract

“…In this way, Keap1 negatively regulates Nrf2, inhibiting its activity and thereby maintaining cell homeostasis. When exposed to poisons or certain stimuli, the Keap1-Nrf2 dimer is automatically separated, and Nrf2 is activated and transferred to the nucleus to bind to ARE, thereby activating the expression of antioxidant enzymes and phase II detoxification enzyme genes [ 44 , 45 ]. Therefore, the decrease of antioxidant enzyme activity and the increase of GPX1 expression in intestinal oxidative stress induced by ZEA may be the result of an oxidative stress signal induced by the Keap1-Nrf2 signaling pathway and the regulation of antioxidant enzyme expression by the transcription factor Nrf2.…”

Section: Discussionmentioning

confidence: 99%

Zearalenone regulates key factors of the Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1–nuclear factor erythroid 2-related factor 2 signaling pathway in duodenum of post-weaning gilts

et al. 2021

View full text Add to dashboard Cite

Objective: This study explored the mechanism of the Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor (Nrf2) signaling pathway under conditions of ZEA-induced oxidative stress in the duodenum of post-weaning gilts. Methods: Forty post-weaning gilts were randomly allocated to four groups and fed diets supplemented with 0, 0.5, 1.0, or 1.5 mg/kg ZEA. Results: The results showed significant reductions in the activity of the antioxidant enzymes total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px), and increases the malondialdehyde (MDA) content with increasing concentrations of dietary ZEA. Immunohistochemical analysis supported these findings by showing a significantly increased expression of Nrf2 and glutathione peroxidase 1 (GPX1) with increasing concentrations of ZEA. The relative mRNA and protein expression of Nrf2, GPX1 increased linearly (p<0.05) and quadratically (p<0.05), which was consistent with the immunohistochemical results. The relative mRNA expression of Keap1 decreased linearly (p<0.05) and quadratically (p<0.05) in the duodenum as the ZEA concentration increased in the diet. The relative mRNA expression of modifier subunit of glutamate-cysteine ligase (GCLM) increased quadratically (p<0.05) in all ZEA treatment groups and the relative mRNA expression of quinone oxidoreductase 1 (NQO1) catalytic subunit of glutamate-cysteine ligase (GCLC) decreased linearly (p<0.05) and quadratically (p<0.05) in the ZEA1.0 group and ZEA1.5 group. The relative protein expression of Keap1 and GCLM decreased quadratically (p<0.05) in the duodenum as the ZEA concentration increased in the diet, respectively. The relative protein expression of NQO1 increased linearly (p<0.05) and quadratically (p<0.05) in all ZEA treatment groups in the duodenum. Conclusion: These findings suggest that ZEA regulates the expression of key factors of the Keap1-Nrf2 signaling pathway in the duodenum, which enables resistance to ZEA-induced oxidative stress. Further studies are needed to examine the effects of ZEA-induced oxidative stress on other tissues and organs in post-weaning gilts.

show abstract

GSTA3 regulates TGF-β1-induced renal interstitial fibrosis in NRK-52E cells as a component of the PI3K–Keap1/Nrf2 pathway

Cited by 9 publications

References 26 publications

Identification of Novel Genes for Cell Fusion during Osteoclast Formation

Identification of Novel Genes for Cell Fusion during Osteoclast Formation

Yi-Shen-Hua-Shi Granule Alleviates Adriamycin-Induced Glomerular Fibrosis by Suppressing the BMP2/Smad Signaling Pathway

Zearalenone regulates key factors of the Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1–nuclear factor erythroid 2-related factor 2 signaling pathway in duodenum of post-weaning gilts

Contact Info

Product

Resources

About