scholarly journals Loss of miR-24-3p promotes epithelial cell apoptosis and impairs the recovery from intestinal inflammation

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Artin Soroosh ◽  
Kai Fang ◽  
Jill M. Hoffman ◽  
Ivy K. M. Law ◽  
Elizabeth Videlock ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Cell Apoptosis ◽  
Intestinal Inflammation ◽  
Loss Of Function ◽  
Epithelial Cell Apoptosis ◽  
Vitro Analysis ◽  
Double Blinded ◽  
Active Inflammation

AbstractWhile apoptosis plays a significant role in intestinal homeostasis, it can also be pathogenic if overactive during recovery from inflammation. We recently reported that microRNA-24-3p (miR-24-3p) is elevated in the colonic epithelium of ulcerative colitis patients during active inflammation, and that it reduced apoptosis in vitro. However, its function during intestinal restitution following inflammation had not been examined. In this study, we tested the influence of miR-24-3p on mucosal repair by studying recovery from colitis in both novel miR-24-3p knockout and miR-24-3p-inhibited mice. We observed that knockout mice and mice treated with a miR-24-3p inhibitor had significantly worsened recovery based on weight loss, colon length, and double-blinded histological scoring. In vivo and in vitro analysis of miR-24-3p inhibition in colonic epithelial cells revealed that inhibition promotes apoptosis and increases levels of the pro-apoptotic protein BIM. Further experiments determined that silencing of BIM reversed the pro-apoptotic effects of miR-24-3p inhibition. Taken together, these data suggest that miR-24-3p restrains intestinal epithelial cell apoptosis by targeting BIM, and its loss of function is detrimental to epithelial restitution following intestinal inflammation.

scholarly journals Effects of a progestogen on normal human breast epithelial cell apoptosis in vitro and in vivo

The Breast ◽  
2003 ◽  
Vol 12 (2) ◽  
pp. 142-149 ◽  
Author(s):  
J Desreux ◽  
F Kebers ◽  
A Noël ◽  
D Francart ◽  
H Van Cauwenberge ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Cell Apoptosis ◽  
Breast Epithelial Cell ◽  
Human Breast ◽  
Human Breast Epithelial Cell ◽  
Normal Human Breast ◽  
Epithelial Cell Apoptosis ◽  
Normal Human

scholarly journals Mammalian STE20-Like Kinase 1 Deletion Alleviates Renal Ischaemia-Reperfusion Injury via Modulating Mitophagy and the AMPK-YAP Signalling Pathway

2018 ◽  
Vol 51 (5) ◽  
pp. 2359-2376 ◽  
Author(s):  
Junxia Feng ◽  
Hongyan Li ◽  
Yunfang Zhang ◽  
Qi Wang ◽  
Shili Zhao ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Cell Apoptosis ◽  
Tubular Epithelial Cell ◽  
Signalling Pathway ◽  
Ischaemia Reperfusion Injury ◽  
Renal Ischaemia ◽  
Ischaemia Reperfusion ◽  
Epithelial Cell Apoptosis

Background/Aims: The aim of our study is to investigate the molecular mechanism by which mammalian STE20-like kinase 1 (Mst1) participates in renal I/R injury through modifying mitophagy and the AMPK-YAP signalling pathway. Methods: WT mice and Mst1-knockout mice were subjected to renal ischaemia-reperfusion (I/R) in vivo. In vitro, the hypoxia-reoxygenation model was used with renal tubular epithelial cells to mimic renal I/R injury. Mitochondrial function was monitored via western blotting and immunofluorescence. Pathway blocker and siRNA knockout technology were used to establish the role of the AMPK-YAP signalling pathway in Mst1-mediated mitochondrial apoptosis in the setting of renal I/R injury. Results: Our data demonstrated that Mst1 expression was upregulated in response to renal I/R injury in vivo, and a higher Mst1 content was positively associated with renal dysfunction and more tubular epithelial cell apoptosis. However, genetic ablation of Mst1 improved renal function, alleviated reperfusion-mediated tubular epithelial cell apoptosis, and attenuated the vulnerability of kidney to I/R injury. In vitro, Mst1 upregulation induced mitochondrial damage including mitochondrial potential reduction, ROS overloading, cyt-c liberation and caspase-9 apoptotic pathway activation. At the molecular levels, I/R-mediated mitochondrial damage via repressing mitophagy and Mst1 suppressed mitophagy via inactivating AMPK signalling pathway and dowregulating OPA1 expression. Re-activation of AMPK-YAP-OPA1 signalling pathway provided a survival advantage for the tubular epithelial cell in the context of renal I/R injury by repressing mitochondrial fission. Conclusion: Overall, our results demonstrate that the pathogenesis of renal I/R injury is closely associated with an increase in Mst1 expression and the inactive AMPK-YAP-OPA1 signalling pathway. Based on this, strategies to repress Mst1 expression and activate mitophagy could serve as therapeutic targets to treat kidney ischaemia-reperfusion injury.

scholarly journals Propofol attenuates lung ischemia/reperfusion injury though the involvement of the MALAT1/microRNA-144/GSK3β axis

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Jian-Ping Zhang ◽  
Wei-Jing Zhang ◽  
Miao Yang ◽  
Hua Fang
Keyword(s):  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Glycogen Synthase ◽  
Ischemia Reperfusion ◽  
Inflammatory Factors ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Loss Of Function

Abstract Background Propofol, an intravenous anesthetic, was proven to protect against lung ischemia/reperfusion (I/R) injury. However, the detailed mechanism of Propofol in lung I/R injury is still elusive. This study was designed to explore the therapeutic effects of Propofol, both in vivo and in vitro, on lung I/R injury and the underlying mechanisms related to metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA-144 (miR-144)/glycogen synthase kinase-3β (GSK3β). Methods C57BL/6 mice were used to establish a lung I/R injury model while pulmonary microvascular endothelial cells (PMVECs) were constructed as hypoxia/reperfusion (H/R) cellular model, both of which were performed with Propofol treatment. Gain- or loss-of-function approaches were subsequently employed, followed by observation of cell apoptosis in lung tissues and evaluation of proliferative and apoptotic capabilities in H/R cells. Meanwhile, the inflammatory factors, autophagosomes, and autophagy-related proteins were measured. Results Our experimental data revealed that Propofol treatment could decrease the elevated expression of MALAT1 following I/R injury or H/R induction, indicating its protection against lung I/R injury. Additionally, overexpressing MALAT1 or GSK3β promoted the activation of autophagosomes, proinflammatory factor release, and cell apoptosis, suggesting that overexpressing MALAT1 or GSK3β may reverse the protective effects of Propofol against lung I/R injury. MALAT1 was identified to negatively regulate miR-144 to upregulate the GSK3β expression. Conclusion Overall, our study demonstrated that Propofol played a protective role in lung I/R injury by suppressing autophagy and decreasing release of inflammatory factors, with the possible involvement of the MALAT1/miR-144/GSK3β axis.

scholarly journals Deficiency in the anti-apoptotic protein DJ-1 promotes intestinal epithelial cell apoptosis and aggravates inflammatory bowel disease via p53

2020 ◽  
Vol 295 (13) ◽  
pp. 4237-4251 ◽  
Author(s):  
Jie Zhang ◽  
Min Xu ◽  
Weihua Zhou ◽  
Dejian Li ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Epithelial Cell ◽  
Bowel Disease ◽  
Intestinal Epithelial Cell ◽  
Intestinal Inflammation ◽  
Intestinal Epithelial ◽  
P53 Expression ◽  
Inflammatory Bowel

Parkinson disease autosomal recessive, early onset 7 (PARK7 or DJ-1) is involved in multiple physiological processes and exerts anti-apoptotic effects on multiple cell types. Increased intestinal epithelial cell (IEC) apoptosis and excessive activation of the p53 signaling pathway is a hallmark of inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD). However, whether DJ-1 plays a role in colitis is unclear. To determine whether DJ-1 deficiency is involved in the p53 activation that results in IEC apoptosis in colitis, here we performed immunostaining, real-time PCR, and immunoblotting analyses to assess DJ-1 expression in human UC and CD samples. In the inflamed intestines of individuals with IBD, DJ-1 expression was decreased and negatively correlated with p53 expression. DJ-1 deficiency significantly aggravated colitis, evidenced by increased intestinal inflammation and exacerbated IEC apoptosis. Moreover, DJ-1 directly interacted with p53, and reduced DJ-1 levels increased p53 levels both in vivo and in vitro and were associated with decreased p53 degradation via the lysosomal pathway. We also induced experimental colitis with dextran sulfate sodium in mice and found that compared with DJ-1−/− mice, DJ-1−/−p53−/− mice have reduced apoptosis and inflammation and increased epithelial barrier integrity. Furthermore, pharmacological inhibition of p53 relieved inflammation in the DJ-1−/− mice. In conclusion, reduced DJ-1 expression promotes inflammation and IEC apoptosis via p53 in colitis, suggesting that the modulation of DJ-1 expression may be a potential therapeutic strategy for managing colitis.

scholarly journals Niacin mitigates rumen epithelial damage in vivo by inhibiting rumen epithelial cell apoptosis on a high concentrate diet

2021 ◽  
Author(s):  
Zhen Gao ◽  
Yanjiao Li ◽  
Chao Xu ◽  
Dan Luo ◽  
Qinghua Qiu ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Antioxidant Capacity ◽  
Inflammatory Cytokines ◽  
Cell Apoptosis ◽  
Volatile Fatty Acids ◽  
Epithelial Damage ◽  
Rumen Epithelium ◽  
Rumen Ph ◽  
Epithelial Cell Apoptosis

Abstract To investigate the effects of niacin on rumen fermentation, rumen epithelial antioxidant activity, and rumen epithelial cell apoptosis on high concentrate (HC) diets, nine male Hu sheep were randomly divided into: low concentrate diet (LC; concentrate : forage (C:F) = 20:80, high concentrate diet (HC; C:F = 80:20), and HCN diet (HC diet + niacin at 800 mg/kg diet air-dry matter). Compared with the LC group, the HC group had a lower rumen pH, increased volatile fatty acids and lactic acid in the rumen, reduced activity of antioxidant enzymes and total antioxidant capacity, and increased malondialdehyde content in the rumen epithelium (P < 0.05). Rumen epithelial papilla morphology was decreased, and apoptosis-related indicators and serum inflammatory cytokines were increased in the HC group over the LC group (P < 0.05). Compared with the HC diet, the HCN diet increased rumen pH, rumen epithelium antioxidant capacity, and rumen epithelial papilla morphology, decreased rumen lactate content, serum inflammatory cytokines, and apoptosis-related indicators (P < 0.05). Therefore, adding 800 mg/kg niacin helped protect against rumen epithelial damage by avoiding drastic changes in the rumen environment and improved rumen epithelial antioxidant capacity to inhibit rumen epithelial cell apoptosis in sheep on a HC diet.

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