Intercellular Signalling Cross-Talk: To Kill, To Heal and To Rejuvenate

Plotnikov, Egor Y.; Silachev, D. N.; Popkov, Vasily A.; Zorova, Ljubava D.; Pevzner, Irina B.; Zorov, Savva D.; Jankauskas, Stanislovas S.; Babenko, Valentina A.; Сухих, Г. Т.; Zorov, Dmitry B.

doi:10.1016/j.hlc.2016.12.002

Cited by 25 publications

(21 citation statements)

References 180 publications

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“…The issue of rehabilitation after injury remains one of the important subjects and purposes of the research. The ability to recover lost functions is largely determined both by the rate of elimination of damaged structures (in particular, through the process of autophagy 14 ), mobilization of resident stem cells 15 , 16 and by the activation of signaling regenerative cascades in remaining differentiated cells 17 , 18 . Proliferation factors have been shown to play an important role in the latter processes, many of which are attributed to rejuvenating functions 19 – 22 .…”

Section: Resultsmentioning

confidence: 99%

Pregnancy protects the kidney from acute ischemic injury

Popkov

Andrianova

Манских

et al. 2018

Sci Rep

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A complex analysis of acute kidney injury (AKI) in pregnant women shows that it is caused by the interaction of gestation-associated pathologies and beneficial signaling pathways activated by pregnancy. Studies report an increase in the regeneration of some organs during pregnancy. However, the kidney response to the injury during pregnancy has not been addressed. We investigated the mechanisms of the pregnancy influence on AKI. During pregnancy, the kidneys were shown to be more tolerant to AKI. Pregnant animals showed remarkable preservation of kidney functions after ischemia/reperfusion (I/R) indicated by the decrease of serum creatinine levels. The pregnant rats also demonstrated a significant decrease in kidney injury markers and an increase in protective markers. Two months after the I/R, group of pregnant animals had a decreased level of fibrosis in the kidney tissue. These effects are likely linked to increased cell proliferation after injury: using real-time cell proliferation monitoring we demonstrated that after ischemic injury, cells isolated from pregnant animal kidneys had higher proliferation potential vs. control animals; it was also supported by an increase of proliferation marker PCNA levels in kidneys of pregnant animals. We suggest that these effects are associated with hormonal changes in the maternal organism, since hormonal pseudopregnancy simulated effects of pregnancy.

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Section: Resultsmentioning

confidence: 99%

Pregnancy protects the kidney from acute ischemic injury

Popkov

Andrianova

Манских

et al. 2018

Sci Rep

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“…Intercellular cross‐talk is fundamental for cell function and homeostasis maintenance . EMVs released from ECs upon stress, activation, or apoptosis could deliver proteins and gene messages (mRNA, miRs) to the recipient cells, representing a novel way of cell‐to‐cell communication .…”

Section: Discussionmentioning

confidence: 99%

Microvesicles‐mediated communication between endothelial cells modulates, endothelial survival, and angiogenic function via transferring of miR‐125a‐5p

Pan

Wang

et al. 2018

J of Cellular Biochemistry

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Endothelial cells (ECs) released microvesicles (EMVs) could modulate the functions of target cells by transferring their microRNAs (miRs). We have reported that miR-125a-5p protected EC function. In this study, we determined whether EMVs provided beneficial effects on ECs by transferring miR-125a-5p. Human brain microvessel ECs were transfected with miR-125a-5p mimic or miR-125a-5p short hairpin RNA to obtain miR-125a-5p overexpressing ECs and miR-125a-5p knockdown ECs, and their derived EMVs. For the functional study, ECs or hypoxia/reoxygenation injured ECs were coincubated with various EMVs. The survival and angiogenic function of ECs were measured. Western blot and quantitative real time polymerase chain reaction (qRT-PCR) were used for measuring the levels of phosphoinositide 3-kinase (PI3K), phosphorylation-Akt (p-Akt)/Akt, p-endothelial nitric oxide synthase (p-eNOS), cleaved caspase-3, and miR-125a-5p. PI3K inhibitor was used for pathway analysis. EMVs promoted the proliferation, migration, and tube formation ability of ECs, and alleviated the apoptotic rate of ECs. These effects were associated by an increase in p-Akt/Akt and p-eNOS, and a decrease in cleaved caspase-3 could be abolished by LY294002. Overexpression or downregulation of miR-125a-5p in EMVs promoted or inhibited those effects of EMVs. EMVs could enhance the survival and angiogenic function of ECs via delivering miR-125a-5p to modulate the expression of PI3K/Akt/eNOS pathway and caspase-3. K E Y W O R D S brain endothelial cells (ECs), cell function, hypoxia and reperfusion, microvesicles (MVs), miR-125a-5p J Cell Biochem. 2019;120:3160-3172. wileyonlinelibrary.com/journal/jcb 3160 |

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“…For example, cellular homeostasis is predominantly determined by both the functionality and integrity of molecules such as enzymes within the cell [10–12]. Individual functions of the constituent cells and intercellular signaling aid in maintaining tissue homeostasis [10, 13, 14]. In case of tissue dysfunction within one organ system, the surrounding tissues can compensate appropriately to maintain organ functionality [15–17].…”

Section: Introductionmentioning

confidence: 99%

Organ system network analysis and biological stability in critically ill patients

et al. 2019

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BackgroundContinuous coordination among organ systems is necessary to maintain biological stability in humans. Organ system network analysis in addition to organ-oriented medicine is expected to improve patient outcomes. However, organ system networks remain beyond clinical application with little evidence for their importance on homeostatic mechanisms. This proof-of-concept study examined the impact of organ system networks on systemic stability in severely ill patients.MethodsPatients admitted to the intensive care unit of the University of Tokyo Hospital with one representative variable reflecting the condition of each of the respiratory, cardiovascular, renal, hepatic, coagulation, and inflammatory systems were enrolled. Relationships among the condition of individual organ systems, inter-organ connections, and systemic stability were evaluated between non-survivors and survivors whose organ system conditions were matched to those of the non-survivors (matched survivors) as well as between non-survivors and all survivors. We clustered these six organ systems using principal component analysis and compared the dispersion of the principal component scores of each cluster using the Ansari-Bradley test to evaluate systemic stability involving multiple organ systems. Inter-organ connections were evaluated using Spearman’s rank test.ResultsAmong a total of 570 enrolled patients, 91 patients died. The principal component analysis yielded the respiratory-renal-inflammatory and cardiovascular-hepatic-coagulation system clusters. In the respiratory-renal-inflammatory cluster, organ systems were connected in both the survivors and the non-survivors. The principal component scores of the respiratory-renal-inflammatory cluster were dispersed similarly (stable cluster) in the non-survivors, the matched survivors, and the total survivors irrespective of the severity of individual organ system dysfunction. Conversely, in the cardiovascular-hepatic-coagulation cluster, organ systems were connected only in the survivors, and the principal component scores of the cluster were significantly dispersed (unstable cluster) in the non-survivors compared to the total survivors (P = 0.002) and the matched survivors (P = 0.004).ConclusionsThis study demonstrated that systemic instability was closely associated with network disruption among organ systems irrespective of their dysfunction severity. Organ system network analysis is necessary to improve outcomes in severely ill patients.Electronic supplementary materialThe online version of this article (10.1186/s13054-019-2376-y) contains supplementary material, which is available to authorized users.

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Intercellular Signalling Cross-Talk: To Kill, To Heal and To Rejuvenate

Cited by 25 publications

References 180 publications

Pregnancy protects the kidney from acute ischemic injury

Pregnancy protects the kidney from acute ischemic injury

Microvesicles‐mediated communication between endothelial cells modulates, endothelial survival, and angiogenic function via transferring of miR‐125a‐5p

Organ system network analysis and biological stability in critically ill patients

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