Celastrol induces ferroptosis in activated HSCs to ameliorate hepatic fibrosis via targeting peroxiredoxins and HO-1

Luo, Piao; Liu, Dandan; Zhang, Qian; Yang, Fan; Wong, Yin‐Kwan; Xia, Fei; Zhang, Junzhe; Chen, Jiayun; Tian, Ya; Yang, Chonglin; Dai, Lingyun; Shen, Han‐Ming; Wang, Jigang

doi:10.1016/j.apsb.2021.12.007

Cited by 153 publications

(73 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Next, it was necessary to investigatewhether pyroptosis and ferroptosis are involved in pathological myeloid differentiation. Myeloid cells in CD patients highly express anti-ferroptosis genes, such as GPX4, NFE2L2, FTH1, FTL, P4HB [67], and PRDX1 [68]. Moreover, compared to healthy myeloid cells, these myeloid cells expressed NCOA4 at low levels.…”

Section: Ferroptosis Was Involved In the Imbalance Of Intestinal Micr...mentioning

confidence: 99%

Evidence of pyroptosis and ferroptosis extensively involved in autoimmune diseases at the single-cell transcriptome level

Zhang

et al. 2022

J Transl Med

View full text Add to dashboard Cite

Background Approximately 8–9% of the world’s population is affected by autoimmune diseases, and yet the mechanism of autoimmunity trigger is largely understudied. Two unique cell death modalities, ferroptosis and pyroptosis, provide a new perspective on the mechanisms leading to autoimmune diseases, and development of new treatment strategies. Methods Using scRNA-seq datasets, the aberrant trend of ferroptosis and pyroptosis-related genes were analyzed in several representative autoimmune diseases (psoriasis, atopic dermatitis, vitiligo, multiple sclerosis, systemic sclerosis-associated interstitial lung disease, Crohn’s disease, and experimental autoimmune orchitis). Cell line models were also assessed using bulk RNA-seq and qPCR. Results A substantial difference was observed between normal and autoimmune disease samples involving ferroptosis and pyroptosis. In the present study, ferroptosis and pyroptosis showed an imbalance in different keratinocyte lineages of psoriatic skinin addition to a unique pyroptosis-sensitive keratinocyte subset in atopic dermatitis (AD) skin. The results also revealed that pyroptosis and ferroptosis are involved in epidermal melanocyte destruction in vitiligo. Aberrant ferroptosis has been detected in multiple sclerosis, systemic sclerosis-associated interstitial lung disease, Crohn’s disease, and autoimmune orchitis. Cell line models adopted in the study also identified pro-inflammatory factors that can drive changes in ferroptosis and pyroptosis. Conclusion These results provide a unique perspective on the involvement of ferroptosis and pyroptosis in the pathological process of autoimmune diseases at the scRNA-seq level. IFN-γ is a critical inducer of pyroptosis sensitivity, and has been identified in two cell line models.

show abstract

Section: Ferroptosis Was Involved In the Imbalance Of Intestinal Micr...mentioning

confidence: 99%

Evidence of pyroptosis and ferroptosis extensively involved in autoimmune diseases at the single-cell transcriptome level

Zhang

et al. 2022

J Transl Med

View full text Add to dashboard Cite

show abstract

“…Beads were enriched with protein and then separated using SDS-PAGE, followed by detection using western blotting. For the identification of target proteins using LC-MS/MS [ 28 ], the specific molecular weight bands were excised and washed, and the samples were reduced and alkylated using dithiothreitol and iodoacetamide, respectively. Subsequently, proteins were digested into peptides using trypsin.…”

Section: Methodsmentioning

confidence: 99%

18beta-glycyrrhetinic acid induces ROS-mediated apoptosis to ameliorate hepatic fibrosis by targeting PRDX1/2 in activated HSCs

Zhang

Luo

Zheng

et al. 2022

Journal of Pharmaceutical Analysis

Self Cite

View full text Add to dashboard Cite

“…Celastrol also targets heme oxygenase 1 (HO-1) and upregulates its expression in activated HSC. Knockdown of PRDX1, PRDX2, PRDX4, PRDX6 or HO-1 in HSC differentially elevated cellular ROS levels and induced iron death (Figure 4) [212] .…”

Section: Celastrolmentioning

confidence: 99%

Small-molecule natural products for reversing liver fibrosis based on modulation of HSCs activation: an update

Zheng

Yang

Luo

et al. 2022

Preprint

View full text Add to dashboard Cite

Liver fibrosis (LF) is a trauma repair process carried out by the liver in response to various acute and chronic liver injuries, featured by excessive proliferation as well as abnormal dismissal of extracellular matrix as the main pathological features, and its continuous development will deteriorate into cirrhosis, liver cancer as well as other illnesses. The occurrence of LF is closely related to Hepatic stellate cells (HSCs) stimulation, and intervention in HSCs proliferation is expected to reverse LF. Plant-based small molecule drugs have anti-LF effects, and their mechanisms of action are related to anti-inflammation, anti-oxidative stress, as well as inhibition of abnormal accumulation of extracellular matrix. Consequently, new agents for HSCs will be required to furnish a possible curative response. Small-molecule natural products might be attractive for LF therapy. That is because they not only have the effect against HSCs, but also have excellent qualities such as low toxic side effects and easy availability from the perspective of safety and cost. In this review, we provide an updated review of the signal transduction pathways involved in HSCs and small-molecule natural products targeting HSCs reported in the past 3 years at home and abroad, with the aim of providing new ideas for the development of plant-based small molecule drugs targeting HSCs to reverse LF.

show abstract

Celastrol induces ferroptosis in activated HSCs to ameliorate hepatic fibrosis via targeting peroxiredoxins and HO-1

Cited by 153 publications

References 64 publications

Evidence of pyroptosis and ferroptosis extensively involved in autoimmune diseases at the single-cell transcriptome level

Evidence of pyroptosis and ferroptosis extensively involved in autoimmune diseases at the single-cell transcriptome level

18beta-glycyrrhetinic acid induces ROS-mediated apoptosis to ameliorate hepatic fibrosis by targeting PRDX1/2 in activated HSCs

Small-molecule natural products for reversing liver fibrosis based on modulation of HSCs activation: an update

Contact Info

Product

Resources

About