miR-34b-5p promotes renal cell inflammation and apoptosis by inhibiting aquaporin-2 in sepsis-induced acute kidney injury

Zheng, Caifa; Wu, Dansen; Shu, Shi; Wang, Liming

doi:10.1080/0886022x.2021.1871922

Cited by 25 publications

(21 citation statements)

References 33 publications

(31 reference statements)

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“…In addition, GAFP levels and pro-inflammatory cytokine IL-1β secretion increased after AQP2 overexpression. This result is consistent with those of previous studies reporting that AQP2 influences not only fluid transport but also cytokine release (e.g., IL-6, TNFα, IL-1β) ( 13 ). TLR4, an essential member of the TLR family involved in innate immunity, is mainly expressed in astrocytes or microglia and contributes greatly to cytokine production after ICH ( 43 ).…”

Section: Discussionsupporting

confidence: 93%

“…In addition to AQPs, AQP2 participates in the regulation of inflammation and apoptosis in renal diseases. As an upstream regulator, AQP2 suppresses LPS-induced renal inflammatory response by reducing the levels of TNF-α, IL-1β, and IL-6 ( 13 ). AQP2 also acts as a downstream effector of inflammation; for example, the Nod-like receptor protein 3 (NLRP3)-induced inflammatory response can decrease AQP2 expression in chronic kidney disease (CKD) ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

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AQP2 Promotes Astrocyte Activation by Modulating the TLR4/NFκB-p65 Pathway Following Intracerebral Hemorrhage

et al. 2022

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Microglial and astrocyte activation and related cytokine secretion play key roles in secondary brain injury following intracerebral hemorrhage (ICH). We assessed the role of aquaporin (AQP)2 in immune response after ICH. We prospectively collected data from 33 patients with ICH and analyzed the serum AQP2 levels in these patients and age-matched healthy controls. A correlation analysis was also performed between patient serum AQP2 levels and clinical factors. In the rat ICH model, double-fluorescence staining for glial fibrillary acidic protein (GFAP) and AQP2 was performed to investigate the relationship between astrocytes and AQP2. Relative mRNA expression levels of GFAP and AQP2 were also measured. In the rat astrocyte cell line CTX-TNA2, toll-like receptor (TLR)4/nuclear factor kappa B (NFκB)-p65 pathway activation and GFAP levels were measured. The indirect influence of AQP2 on microglial polarization was assessed following exposure to the medium of astrocytes treated with AQP2-overexpression plasmid or silencing RNA. We found that the serum AQP2 expression was lower in patients with ICH. Sex and blood neutrophil count influenced serum AQP2 concentrations in patients with ICH on admission. Lower serum AQP2 levels were inversely correlated with 90-day Modified Rankin Scale scores after ICH, but were not correlated with National Institute of Health stroke scale (NIHSS) scores on admission. AQP2 overexpression and localization in GFAP-labeled astrocytes were observed in rats. AQP2 overexpression induced astrocyte activation with GFAP upregulation via TLR/NFκB-p65 signaling pathway activation in the rat astrocyte cell line CTX-TNA2. Astrocyte activation promoted interleukin-1β secretion. The medium of AQP2-overexpression astrocytes promoted the pro-inflammatory M1 phenotype in the immortal rat (HAPI) microglial cell line. Therefore, serum AQP2 is negatively correlated with post-ICH prognosis and may be a marker of inflammation in early-stage ICH. AQP2 overexpression promotes astrocyte activation and pro-inflammatory secretion, affects astrocyte-microglia crosstalk, and indirectly induces microglial polarization, which may augment inflammation after ICH.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

AQP2 Promotes Astrocyte Activation by Modulating the TLR4/NFκB-p65 Pathway Following Intracerebral Hemorrhage

et al. 2022

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“…However, sepsis can occur when inflammatory cytokines are produced uncontrolled and beyond the scope of the local infections environment and cause a broader response. 12 …”

Section: Discussionmentioning

confidence: 99%

“…Among many miRNAs, miR-486-5p is located on human chromosome 8p11.21 and can be used as a potential biomarker for sarcopenia in the elderly, 9 endometrial cancer, 10 and chronic myelogenous leukemia. 11 What is more, inflammation is involved in the pathogenesis of sepsis, 12 and miR-486-5p as an inflammation regulator has been confirmed in many diseases. Such as miR-486-5p regulates polycystic ovary syndrome by regulating inflammation.…”

Section: Introductionmentioning

confidence: 99%

miR-486-5p Serves as a Diagnostic Biomarker for Sepsis and Its Predictive Value for Clinical Outcomes

Sun

Guo

2021

JIR

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Background As a molecular detection method, miRNA can quickly diagnose and prevent diseases, intervene in disease as early as possible, and reduce mortality. This study was to investigate the potential clinical diagnostic and predictive significance of miR-486-5p in sepsis and its correlation with inflammation and disease severity. Methods The serum miR-486-5p in 108 sepsis, 60 pneumonia-infected, and 101 healthy controls were detected by RT-qPCR. Spearman coefficient detects the correlation between serum miRNA and disease severity indicators (APACHE II, SOFA scores), and inflammation indicators (CRP, PCT), respectively. The diagnostic significance of miR-486-5p in sepsis was analyzed by the ROC curve. Kaplan–Meier estimator and Cox regression hazards analysis of the predictive significance of serum miR-486-5p in 28-day survival from sepsis. Results Serum miR-486-5p was increased in sepsis patients compared with healthy control and pneumonia-infected patients ( P < 0.001). And increased serum miR-486-5p was positively associated with disease severity (SOFA score and APACHE II score) and inflammation (CRP and PCT). Serum miR-486-5p can not only identify sepsis patients from healthy controls (AUC = 0.914) but also significantly distinguish sepsis patients from pneumonia-infected patients (AUC = 0.814), showing good potential as a diagnostic biomarker for sepsis. In addition, serum miR-486-5p was an independent predictor of 28-day survival (log-rank P = 0.012), and patients with high levels of miR-486-5p had a poorer overall 28-day survival (HR = 3.057, 95% CI = 1.385–17.817, P = 0.014). Conclusion miR-486-5p is a potential diagnostic biomarker for sepsis, and its high level is significantly correlated with the disease severity and inflammation. In addition, miR-486-5p were predictive risk factors for 28-day survival in sepsis patients.

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“…This review did not identify direct analyses of inflammasome components in human S-AKI. Increased concentrations of serum IL-1β protein concentration in S-AKI have been reported [ 172 , 173 ]. On the other hand, elevations of IL-1β serum concentrations in human sepsis can be mild [ 174 ] or irregular [ 175 ], are dependent on the phase of septic state [ 176 ], and, in addition, the kidney has a role in IL-1β removal in sepsis as long as diuresis is preserved [ 177 ].…”

Section: Inflammasome Components In Akimentioning

confidence: 99%

Involvement of Inflammasome Components in Kidney Disease

et al. 2022

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Inflammasomes are multiprotein complexes with an important role in the innate immune response. Canonical activation of inflammasomes results in caspase-1 activation and maturation of cytokines interleukin-1β and -18. These cytokines can elicit their effects through receptor activation, both locally within a certain tissue and systemically. Animal models of kidney diseases have shown inflammasome involvement in inflammation, pyroptosis and fibrosis. In particular, the inflammasome component nucleotide-binding domain-like receptor family pyrin domain containing 3 (NLRP3) and related canonical mechanisms have been investigated. However, it has become increasingly clear that other inflammasome components are also of importance in kidney disease. Moreover, it is becoming obvious that the range of molecular interaction partners of inflammasome components in kidney diseases is wide. This review provides insights into these current areas of research, with special emphasis on the interaction of inflammasome components and redox signalling, endoplasmic reticulum stress, and mitochondrial function. We present our findings separately for acute kidney injury and chronic kidney disease. As we strictly divided the results into preclinical and clinical data, this review enables comparison of results from those complementary research specialities. However, it also reveals that knowledge gaps exist, especially in clinical acute kidney injury inflammasome research. Furthermore, patient comorbidities and treatments seem important drivers of inflammasome component alterations in human kidney disease.

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miR-34b-5p promotes renal cell inflammation and apoptosis by inhibiting aquaporin-2 in sepsis-induced acute kidney injury

Cited by 25 publications

References 33 publications

AQP2 Promotes Astrocyte Activation by Modulating the TLR4/NFκB-p65 Pathway Following Intracerebral Hemorrhage

AQP2 Promotes Astrocyte Activation by Modulating the TLR4/NFκB-p65 Pathway Following Intracerebral Hemorrhage

miR-486-5p Serves as a Diagnostic Biomarker for Sepsis and Its Predictive Value for Clinical Outcomes

Involvement of Inflammasome Components in Kidney Disease

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