scholarly journals Lnc-NEAT1 induces cell apoptosis and inflammation but inhibits proliferation in a cellular model of hepatic ischemia/reperfusion injury

2021 ◽  
Vol 49 (3) ◽  
pp. 030006051988725
Author(s):  
Liu Wang ◽  
Pan Qu ◽  
Wanling Yin ◽  
Jiao Sun
Keyword(s):  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Hepatocyte Proliferation ◽  
Western Blot Assay ◽  
Hepatic Ischemia ◽  
Hepatic Ischemia Reperfusion ◽  
Apoptosis And Inflammation ◽  
Related Proteins

Objective We aimed to investigate the effect of long non-coding RNA nuclear-enriched abundant transcript 1 (lnc-NEAT1) on regulating hepatocyte proliferation, apoptosis, and inflammation during hepatic ischemia/reperfusion (I/R) injury. Methods Human liver cells (HL-7702) were cultured under glucose-free and oxygen-free conditions to construct the I/R injury model. Expression of lnc-NEAT1 was detected in this model and in normal cells. Plasmids of control overexpression [NC(+)], lnc-NEAT1 overexpression [NEAT1(+)], control short hairpin (sh)RNA [NC(−)], and lnc-NEAT1 shRNA [NEAT1(−)] were transfected into HL-7702 cells and subsequently subjected to I/R treatment. Cell proliferation, apoptosis, apoptosis-related proteins, and inflammatory cytokines were assessed. Results Lnc-NEAT1 expression was elevated in the I/R group compared with the normal group. Cell proliferation was decreased in the NEAT1(+) group compared with the NC(+) group but increased in NEAT1(−) compared with NC(−). The apoptosis rate increased in the NEAT1(+) group compared with the NC(+) group but decreased in NEAT1(−) compared with NC(−). Western blot assay (detection of apoptosis-related proteins) showed similar results. Expression of interleukin-1β, interleukin-6, and tumor necrosis factor-α increased in the NEAT1(+) group compared with NC(+) but decreased in NEAT1(−) compared with NC(−). Conclusion Lnc-NEAT1 is overexpressed, induces cell apoptosis and inflammation, and inhibits proliferation during hepatic I/R injury.

scholarly journals Downregulating Serine Hydroxymethyltransferase 2 Deteriorates Hepatic Ischemia-Reperfusion Injury through ROS/JNK/P53 Signaling in Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Hao Wu ◽  
He Bai ◽  
Shigang Duan ◽  
Fangchao Yuan
Keyword(s):  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Liver Weight ◽  
Serine Hydroxymethyltransferase ◽  
Hepatic Ischemia ◽  
P53 Signaling ◽  
Hepatic Ischemia Reperfusion ◽  
P53 Signaling Pathway

Background. Serine hydroxymethyltransferase 2 (SHMT2) activity ensures that cells have a survival advantage in ischemic conditions and regulates redox homeostasis. In this study, we aimed to investigate the role of SHMT2 after hepatic ischemia-reperfusion (IR), which involves hypoxia, ischemic conditions, and cell apoptosis. Methods. A 70% IR model was established in C57BL/6J mice with or without SHMT2 knockdown. H&E staining, liver weight/body weight, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels and cell apoptosis were tested to analyze liver damage and function. Then, the related cellular signals were probed. Results. The level of SHMT2 protein was significantly increased at 24 h and 48 h after IR (p<0.001). Mice in the shSHMT2 group showed more necrotic areas and histological damage at 24 h (p<0.01) after IR and higher levels of serum ALT and AST (p<0.05) compared with those of mice in the scramble group. After IR for 24 h, the expression of TUNEL in the shSHMT2 group was significantly higher than that in the scramble group, as shown by histological analysis (p<0.01). Mechanistically, the JNK/P53 signaling pathway was activated by IR, and knockdown of SHMT2 exacerbated hepatocyte apoptosis. Conclusions. Knockdown of SHMT2 worsens IR injury through the ROS/JNK/P53 signaling pathway. Our discovery expands the understanding of both molecular and metabolic mechanisms involved in IR. SHMT2 is a possible therapeutic target to improve the prognosis of liver transplantation (LT) and subtotal hepatectomy.

scholarly journals Dexmedetomidine Protects against Hepatic Ischemia-Reperfusion Injury by inhibiting Endoplasmic Reticulum Stress and Cell Apoptosis in Rats

2021 ◽  
Author(s):  
Hang Li ◽  
Jilang Tang ◽  
Weiqi Zhang ◽  
Liping Ai ◽  
Shixia Zhang
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Protective Effect ◽  
Reperfusion Injury ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Hepatic Ischemia ◽  
Significant Difference ◽  
Hepatic Ischemia Reperfusion

Abstract Background: Hepatic ischemia-reperfusion injury (IRI) remains a major complication of liver surgery, dexmedetomidine (DEX) has a certain protective effect on liver during ischemia-reperfusion, but the underlying mechanisms are not fully understood. This study explored the protective effects of DEX and investigated whether DEX protects against hepatic IRI by inhibiting endoplasmic reticulum stress (ERS) and its downstream apoptotic pathway in a rat model. Methods: Thirty-six male Sprague-Dawley (SD) rats were divided into six groups: S, IR, DL, DM1, DH and DM2 group. Group S was subjected to laparotomy, and exposure of the portal triad without occlusion. I-R injury model was induced by clamping the portal vessels supplying the middle and left hepatic lobes for 30 min in IR, DL, DM1, DH and DM2 group. Then DL, DM1, DH group received DEX of 25 μg/kg, 50 μg/kg and 100 μg/kg intraperitoneally at 30 min before ischemia, respectively, DM2 group received 50 μg/kg DEX intraperitoneally 30 min after reperfusion, and IR group received normal saline. After 6 h of reperfusion, assessment of liver function, histopathology, oxidative stress was performed. The liver cell microstructure was detected by transmission electron microscopy. Hepatocyte apoptosis was determined by TUNEL assay. Real-time PCR, Western blotting were performed to analyze various ERS molecules. Results: We observed that DEX protected the liver by alleviating hepatocytes damage, reducing the content of ALT and MDA, increasing the activity of SOD, reducing the number of TUNEL-positive cells, down-regulating the expression of GRP-78, PERK, ATF-6, Caspase-12 mRNA, and p-PERK, p-IRE-1 α, CHOP proteins, up-regulating Bcl-2 protein. The effect of 50 μg/kg DEX is superior to 25 μg/kg DEX, but not significantly different from 100μg/kg DEX. There was no significant difference in the above monitoring indexes between DM1 and DM2 group. Conclusions: DEX protects the liver from IRI by inhibiting ERS and cell apoptosis. The protective effect of DEX was dose-dependent in a certain dose range, both DEX administered prior to ischemia and following reperfusion markedly reduced liver injury induced by hepatic IRI in mice.

LncRNA Gm4419 induces cell apoptosis in hepatic ischemia–reperfusion injury via regulating the miR-455–SOX6 axis

2020 ◽  
Vol 98 (4) ◽  
pp. 474-483 ◽  
Author(s):  
Dongjian Ying ◽  
Xinhua Zhou ◽  
Yi Ruan ◽  
Luoluo Wang ◽  
Xiang Wu
Keyword(s):  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Cell Model ◽  
Ischemia Reperfusion ◽  
Annexin V ◽  
Luciferase Reporter ◽  
Hepatic Ischemia ◽  
Hepatic Ischemia Reperfusion

Long non-coding RNA (lncRNA) is known to be involved in a variety of diseases. However, the role of Gm4419 in hepatic ischemia–reperfusion (I/R) injury remains unknown. To study this, we first established a rat model of hepatic I/R, and a BRL-3A cell model of hypoxia–reoxygenation (H/R) for in vivo and in vitro studies. Staining with hematoxylin and eosin and hepatic injury scores were used to evaluate the degree of hepatic I/R injury. Cell apoptosis was assessed via staining with Edu, and with annexin V–FITC–propidium iodide assays. The interactions between Gm4419 and miR-455, as well as miR-455 and SOX6 were evaluated via luciferase reporter activity assays and RNA immunoprecipitation assays. In vivo, we found that Gm4419 was up-regulated in the rats subjected to I/R. Moreover, knockdown of Gm4419 alleviated the I/R-induced liver damage in the rats. In vitro, knockdown of Gm4419 alleviated H/R-induced apoptosis in BRL-3A cells. Interestingly, we found that miR-455 is a target of Gm4419, and Gm4419 regulates the expression of miR-455 via sponging. Furthermore, SOX6 was proven to be the target of miR-455. Finally, rescue experiments confirmed that knockdown of Gm4419 inhibits apoptosis by regulating miR-455 and SOX6 in H/R-treated BRL-3A cells. Therefore, our findings show that the lncRNA Gm4419 accelerates hepatic I/R injury by targeting the miR-455–SOX6 axis, which suggests a novel therapeutic target for hepatic I/R injury.

scholarly journals MALAT1 Promotes Cell Apoptosis and Suppresses Cell Proliferation in Testicular Ischemia-Reperfusion Injury by Sponging MiR-214 to Modulate TRPV4 Expression

2018 ◽  
Vol 46 (2) ◽  
pp. 802-814 ◽  
Author(s):  
Wei Li ◽  
Jin-zhuo Ning ◽  
Fang  Cheng ◽  
Wei-min Yu ◽  
Ting Rao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Western Blot ◽  
Reperfusion Injury ◽  
Real Time Pcr ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Quantitative Real Time Pcr ◽  
Lncrna Malat1 ◽  
Related Proteins

Background/Aims: Accumulating evidences has indicated that aberrant expression of long non-coding RNAs (lncRNAs) is tightly associated with the progression of ischemia-reperfusion injury (IRI). Previous studies have reported that lncRNA MALAT1 regulates cell apoptosis and proliferation in myocardial and cerebral IRI. However, the underlying mechanism of MALAT1 in testicular IRI has not been elucidated. Methods: The levels of MALAT1, some related proteins and apoptosis in the testicular tissues were determined by quantitative real-time PCR, HE staining, immunohistochemistry, western blot and TUNEL assays. Relative expression of MALAT1, miR-214 and related proteins in cells were measured by western blot and quantitative real-time PCR. Cell viability and apoptosis were examined using MTT assay and flow cytometry. Results: In the present study, we found that MALAT1 was up-regulated in animal samples and GC-1 cells. The expression level of MALAT1 was positively related to cell apoptosis and negatively correlated with cell proliferation as testicular IRI progressed. In gain and loss of function assays, we confirmed that MALAT1 promotes cell apoptosis and suppresses cell proliferation in vitro and in vivo. Furthermore, we found that MALAT1 negatively regulates expression of miR-214 and promotes TRPV4 expression at the post-transcriptional level. Consequently, we investigated the correlation between MALAT1 and miR-214 and identified miR-214 as a direct target of MALAT1. In addition, we found that TRPV4 acted as a target of miR-214. Over-expression of miR-214 efficiently abrogated the up-regulation of TRPV4 induced by MALAT1, suggesting that MALAT1 positively regulates the expression of TRPV4 by sponging miR-214. Conclusion: In sum, our study indicated that the lncRNA MALAT1 promotes cell apoptosis and suppresses cell proliferation in testicular IRI via miR-214 and TRPV4.

scholarly journals Is Aryl Hydrocarbon Receptor Antagonism After Ischemia Effective in Alleviating Hepatic Ischemia-Reperfusion Injury in Rats?

2021 ◽  
Author(s):  
Jae-Im Kwon ◽  
Hwon Heo ◽  
Yeon Ji Chae ◽  
Joongkee Min ◽  
Do-Wan Lee ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Aryl Hydrocarbon Receptors ◽  
Hepatic Ischemia ◽  
Aryl Hydrocarbon ◽  
Hepatic Ischemia Reperfusion ◽  
Related Proteins ◽  
Area Percentage ◽  
The Brain

Abstract Aryl hydrocarbon receptors (AhRs) have been reported to be important mediators of ischemic injury in the brain. Furthermore, the pharmacological inhibition of AhR activation after ischemia has been shown to attenuate cerebral ischemia-reperfusion (IR) injury. Here, we investigated whether AhR antagonist administration after ischemia was also effective in ameliorating hepatic IR injury. A 70% partial hepatic IR (45-minute ischemia and 24-hour reperfusion) injury was induced in rats. We administered 6,2',4'-trimethoxyflavone (TMF, 5 mg/kg) intraperitoneally 10 minutes after ischemia. Hepatic IR injury was observed using serum, magnetic resonance imaging-based liver function indices, and liver samples. TMF-treated rats showed significantly lower relative enhancement (RE) values and serum alanine aminotransferase (ALT) and aspartate aminotransferase levels than did untreated rats at three hours after reperfusion. After 24 hours of reperfusion, TMF-treated rats had significantly lower RE values, ΔT1 values, serum ALT levels, and necrotic area percentage than did untreated rats. The expression of the apoptosis-related proteins, Bax and cleaved caspase-3, was significantly lower in TMF-treated rats than in untreated rats. This study demonstrated that inhibition of AhR activation after ischemia was effective in ameliorating IR-induced liver injury in rats.

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