Shikonin reduces hepatic fibrosis by inducing apoptosis and inhibiting autophagy via the platelet‑activating factor‑mitogen‑activated protein kinase axis

Song, Min Seok; Zhang, Heng; Chen, Zhitao; Yang, Jinqiang; Li, Jie; Shao, Sue; Liu, Jing

doi:10.3892/etm.2020.9460

Cited by 12 publications

(10 citation statements)

References 23 publications

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“…For example, shikonin was shown to be capable of alleviating LPS-induced renal injury and oxidative damage [ 250 ], high glucose-induced renal tubular epithelial cell injury in vitro [ 251 ], and unilateral ureteral obstruction (UUO)-induced tubular apoptosis and macrophage infiltration [ 252 ]. Similar findings were obtained in experimental models of cardiac dysfunction [ 253 ], acute lung [ 254 , 255 , 256 ], liver [ 257 , 258 , 259 , 260 , 261 , 262 ], and ear injuries [ 263 ]. Shikonin also protected against cerebral ischemia/reperfusion- and autoimmune encephalomyelitis-induced brain injury through reducing oxidative stress [ 264 , 265 ] and protected microglial cells against LPS-induced cell death [ 266 ] ( Figure 4 B ).…”

Section: Emerging Areas Of Research Involving Pkm2supporting

confidence: 78%

The Role of PKM2 in Metabolic Reprogramming: Insights into the Regulatory Roles of Non-Coding RNAs

Puckett

Alquraishi

Chowanadisai

et al. 2021

IJMS

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Pyruvate kinase is a key regulator in glycolysis through the conversion of phosphoenolpyruvate (PEP) into pyruvate. Pyruvate kinase exists in various isoforms that can exhibit diverse biological functions and outcomes. The pyruvate kinase isoenzyme type M2 (PKM2) controls cell progression and survival through the regulation of key signaling pathways. In cancer cells, the dimer form of PKM2 predominates and plays an integral role in cancer metabolism. This predominance of the inactive dimeric form promotes the accumulation of phosphometabolites, allowing cancer cells to engage in high levels of synthetic processing to enhance their proliferative capacity. PKM2 has been recognized for its role in regulating gene expression and transcription factors critical for health and disease. This role enables PKM2 to exert profound regulatory effects that promote cancer cell metabolism, proliferation, and migration. In addition to its role in cancer, PKM2 regulates aspects essential to cellular homeostasis in non-cancer tissues and, in some cases, promotes tissue-specific pathways in health and diseases. In pursuit of understanding the diverse tissue-specific roles of PKM2, investigations targeting tissues such as the kidney, liver, adipose, and pancreas have been conducted. Findings from these studies enhance our understanding of PKM2 functions in various diseases beyond cancer. Therefore, there is substantial interest in PKM2 modulation as a potential therapeutic target for the treatment of multiple conditions. Indeed, a vast plethora of research has focused on identifying therapeutic strategies for targeting PKM2. Recently, targeting PKM2 through its regulatory microRNAs, long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) has gathered increasing interest. Thus, the goal of this review is to highlight recent advancements in PKM2 research, with a focus on PKM2 regulatory microRNAs and lncRNAs and their subsequent physiological significance.

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Section: Emerging Areas Of Research Involving Pkm2supporting

confidence: 78%

The Role of PKM2 in Metabolic Reprogramming: Insights into the Regulatory Roles of Non-Coding RNAs

Puckett

Alquraishi

Chowanadisai

et al. 2021

IJMS

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“…Song et al found that activated the MAPK signaling pathway could block the development of liver fibrosis by enhancing cell apoptosis and reducing autophagy. 37 Most HCCs (80–90%) develop on underlying chronic liver disease, the main causes include chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections. In South-East Asia and Central Africa, the endemic prevalence of chronic HBV infections accounts for 70% of HCC.…”

Section: Discussionmentioning

confidence: 99%

Construction of a Prognostic Model for Hepatocellular Carcinoma Based on Immunoautophagy-Related Genes and Tumor Microenvironment

Sun

et al. 2021

IJGM

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Background:The aim of this study was to screen and identify immunoautophagy-related genes (IARGs) in HCC patients and clarify their potential prognostic value in HCC patients. Methods: Immune-related genes and autophagy-related gene were downloaded from public databases. Cox regression analysis was used to selected several immunoautophagy-related genes to establish a prognostic model, and patients were divided into high-and low-risk groups based on median risk score. We analyzed the overall survival and clinicopathological characteristics between two groups. Meanwhile, internal validation dataset and external ICGC dataset were used to verify robustness of the model. Associations between six immune cells infiltrates and risk score were analyzed. Results: A prognostic model was established based on CANX and HDAC1. The prognoses of the high-risk group were worse than low-risk group in both TCGA and ICGC datasets. Multivariate Cox regression analysis showed that risk score was an independent prognostic factor for HCC patients. Results showed that the risk score in young group was higher than elderly group. Patients with poorly differentiated tumor may have high risk score and poor survival. The score was positively correlated with immune cells. Conclusion:Our study shows that immunoautophagy-related genes have potential prognostic value for patients with HCC and may provide new information and direction for targeted therapy.

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“…The deregulation of autophagy has been associated with several liver diseases and its regulation has been recognized as a potential novel treatment strategy (39). However, the results of studies investigating the effects of autophagy on liver fibrosis or cirrhosis are contradictory (40)(41)(42)(43)(44). A number of studies have suggested that autophagy prevents the development of liver fibrosis (41,44).…”

Section: Discussionmentioning

confidence: 99%

“…However, the results of studies investigating the effects of autophagy on liver fibrosis or cirrhosis are contradictory (40)(41)(42)(43)(44). A number of studies have suggested that autophagy prevents the development of liver fibrosis (41,44). On the other hand, other studies have demonstrated that autophagy promotes the progression of hepatic fibrosis (42,43).…”

Section: Discussionmentioning

confidence: 99%

Anti‑inflammation treatment for protection of hepatocytes and amelioration of hepatic fibrosis in rats

et al. 2021

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Chronic inflammation is considered as an important pathophysiologic mechanism of hepatic cirrhosis, which induces hepatocyte injury and activates hepatic stellate cells (HSCs), thus resulting in hepatic fibrosis. Previous studies have reported that cyclooxygenase-2 (COX-2) inhibitor can effectively treat liver fibrosis, while somatostatin (SST) analogues inhibit the activation of HSCs. The present study aimed to investigate the effects of a COX-2 inhibitor, celecoxib, combined with a SST analogue, octreotide, for protection of hepatocytes and prevention of fibrosis in a rat model of hepatic fibrosis. Therefore, a hepatic fibrosis rat model was established following peritoneal injection of thioacetamide (TAA), and the rats were then treated with a combination of celecoxib and octreotide (TAA + C). Immunohistochemistry and western blotting assays were used to assess the expression levels of proteins associated with inflammation, epithelial-mesenchymal transition (EMT), proliferation, apoptosis and autophagy. H&E staining, transmission electron microscopy and scanning electron microscopy were used to evaluate the destruction of hepatocytes. Masson's Trichrome and Sirius Red were used to measure the degree of liver fibrosis. The results demonstrated that, compared with those of the control group, the degree of liver fibrosis and the expression of the intrahepatic inflammation factors were aggravated in the TAA group. Furthermore, the apoptosis rate, EMT and autophagy of hepatocytes were also increased in the TAA group. However, treatment with TAA + C restored the aforementioned increased levels compared with the TAA group. In conclusion, treatment of rats with the combination of celecoxib and octreotide could attenuate the progress of hepatic fibrosis via protection of hepatocytes by reducing apoptosis, EMT and autophagy in hepatocytes.

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Shikonin reduces hepatic fibrosis by inducing apoptosis and inhibiting autophagy via the platelet‑activating factor‑mitogen‑activated protein kinase axis

Cited by 12 publications

References 23 publications

The Role of PKM2 in Metabolic Reprogramming: Insights into the Regulatory Roles of Non-Coding RNAs

The Role of PKM2 in Metabolic Reprogramming: Insights into the Regulatory Roles of Non-Coding RNAs

Construction of a Prognostic Model for Hepatocellular Carcinoma Based on Immunoautophagy-Related Genes and Tumor Microenvironment

Anti‑inflammation treatment for protection of hepatocytes and amelioration of hepatic fibrosis in rats

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