MicroRNA-34a Suppresses Autophagy in Tubular Epithelial Cells in Acute Kidney Injury

Liu, Xiujuan; Hong, Quan; Wang, Zhen; Yu, Yanyan; Zou, Xin; Xu, Li‐Hong

doi:10.1159/000439185

Cited by 49 publications

(37 citation statements)

References 36 publications

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“…This assumption was justified by our observations of elevated miR-34a levels in PBC. Like Nrf2, mir-34a influences the transcription of numerous proteins involved in autophagy, including ATG4B, Beclin-1, LC3B II/I, and Sirtuin-1454647. Moreover, it was shown that aberrant accumulation of p62 in autophagy-deficient mice disrupted the Nrf2-Keap1 interaction, which led to Nrf2 accumulation and liver damage48.…”

Section: Discussionmentioning

confidence: 99%

Protection against oxidative stress mediated by the Nrf2/Keap1 axis is impaired in Primary Biliary Cholangitis

Wasik

Milkiewicz

Kempińska-Podhorodecka

et al. 2017

Sci Rep

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In response to oxidative stress, nuclear factor (erythroid-derived 2)-like2 (Nrf2) induces expression of cytoprotective genes. The Nrf2 pathway is controlled by microRNAs and Kelch-like ECH-associated protein1 (Keap1). Nrf2 is stabilized when Keap1 is degraded through the autophagy pathway in a p62-dependent manner. The inhibition of autophagy causes protein accumulation, and Keap1 is inactivated by binding to p62. We investigated the role of the Nrf2/Keap1 axis in the amelioration of oxidative stress in primary biliary cholangitis (PBC). Liver specimens from patients with PBC, with (n = 24) or without cirrhosis (n = 14), and from controls (n = 16) were used for molecular analyses. We found that Nrf2 protein levels were elevated in PBC compared to controls, but Nrf2 gene expression was significantly reduced in cirrhotic PBC. Nrf2 target gene products, HO-1 and GCLC proteins, were reduced compared to controls and reduction of Nrf2 gene expression was associated with elevated levels of microRNA-132 and microRNA-34a. Both Keap1 and p62 protein levels were substantially increased in PBC compared to controls. PBC was associated with reduced Nrf2 expression and autophagy deterioration and these impairments were more advanced in patients with cirrhosis. Aberrant Nrf2/Keap1 system integrity may affect self-defence mechanisms against oxidative stress in PBC.

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Section: Discussionmentioning

confidence: 99%

Protection against oxidative stress mediated by the Nrf2/Keap1 axis is impaired in Primary Biliary Cholangitis

Wasik

Milkiewicz

Kempińska-Podhorodecka

et al. 2017

Sci Rep

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“…On the other hand, functional studies also indicated that knockdown or restoration of certain miRNAs were able to modulate the progression of AKI (X. Y. Li, Zhang, et al, 2014;X. J. Liu et al, 2015b).…”

Section: Mirnas In Akimentioning

confidence: 99%

Noncoding RNAs in acute kidney injury

Ren

Zhu

et al. 2018

Journal Cellular Physiology

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Acute kidney injury (AKI), caused by various stimuli including ischemia reperfusion, nephrotoxic insult, and sepsis, is characterized by abrupt decline of kidney function. Till now, the molecular mechanisms for AKI have not been fully explored and the effective therapies are still lacking. Noncoding RNAs (ncRNAs), a group of biomolecules function at RNA level, are involved in a wide range of physiopathological processes including AKI. MicroRNAs (miRNAs) are the most extensively studied ncRNAs in AKI. Evidence indicated that miRNAs are altered significantly in various types of AKI. Gain-and-loss-of-function studies demonstrated that miRNAs, such as miR-24, miR-126, miR-494, and miR-687, may bind to the 3'-untranslated region of their target genes to regulate inflammation, programmed cell death, and cell cycle in the injury and repair stages of AKI, indicating their therapeutic potential in AKI. In contrast, functions of long noncoding RNAs and circular RNAs in AKI are hot topics but still largely unknown. Additionally, ncRNAs packaged in exosome can be detected in circulation and urine, they may serve as specific biomarkers for AKI. This review summarized the alteration and functional role of ncRNAs and their therapeutic potential in AKI.

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“…Moreover, miR-855-3p shows seed-complementary sequence to other apoptosis and autophagy-related genes, such as MDM4 , BCL2 , CASPASE2 , and CASPASE3 , leading to the understanding that these small modulators are finely inserted in the complex regulatory network of cellular processes [128]. The phase of vesicle initiation was suppressed by miR-30a/b, miR-376b, miR-17-5p, and miR-216a [129-132] inhibiting BECLIN1 expression; by miR-152 [133] that targets ATG14 ; by miR-101 [134] downregulating RAB5A ; and by miR-24-3p, miR-376b, miR-101, and miR-34a [130, 134-136] that modulates ATG4 . Elongation stage was inhibited by miR-204 that directly targets LC3 [137, 138].…”

Section: Mir and Autophagy In Oamentioning

confidence: 99%

MicroRNAs and Autophagy: Fine Players in the Control of Chondrocyte Homeostatic Activities in Osteoarthritis

D’Adamo

Cetrullo

Minguzzi

et al. 2017

Oxidative Medicine and Cellular Longevity

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Osteoarthritis (OA) is a debilitating degenerative disease of the articular cartilage with a multifactorial etiology. Aging, the main risk factor for OA development, is associated with a systemic oxidative and inflammatory phenotype. Autophagy is a central housekeeping system that plays an antiaging role by supporting the clearance of senescence-associated alterations of macromolecules and organelles. Autophagy deficiency has been related to OA pathogenesis because of the accumulation of cellular defects in chondrocytes. Microribonucleic acids (microRNAs or miRs) are a well-established class of posttranscriptional modulators belonging to the family of noncoding RNAs that have been identified as key players in the regulation of cellular processes, such as autophagy, by targeting their own cognate mRNAs. Here, we present a state-of-the-art literature review on the role of miRs and autophagy in the scenario of OA pathogenesis. In addition, a comprehensive survey has been performed on the functional connections of the miR network and the autophagy pathway in OA by using “microRNA,” “autophagy,” and “osteoarthritis” as key words. Discussion of available evidence sheds light on some aspects that need further investigation in order to reach a more comprehensive view of the potential of this topic in OA.

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MicroRNA-34a Suppresses Autophagy in Tubular Epithelial Cells in Acute Kidney Injury

Cited by 49 publications

References 36 publications

Protection against oxidative stress mediated by the Nrf2/Keap1 axis is impaired in Primary Biliary Cholangitis

Protection against oxidative stress mediated by the Nrf2/Keap1 axis is impaired in Primary Biliary Cholangitis

Noncoding RNAs in acute kidney injury

MicroRNAs and Autophagy: Fine Players in the Control of Chondrocyte Homeostatic Activities in Osteoarthritis

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