Downregulation of MicroRNA-30 Facilitates Podocyte Injury and Is Prevented by Glucocorticoids

Wu, Junnan; Cai, Zheng; Fan, Yun; Zeng, Caihong; Chen, Zhaohong; Qin, Weisong; Zhang, Changming; Zhang, Wanfen; Wang, Xiao; Zhu, Xiaodong; Zhang, Mingchao; Zen, Ke; Liu, Fei

doi:10.1681/asn.2012111101

Cited by 155 publications

(159 citation statements)

References 43 publications

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“…The expressions and functions of miR-196a, miR-30a, and miR-490 miRNAs in their respective tissues also support a role for these miRNAs as potential biomarkers of FSGS disease activity. Previous studies, including ours (22,27), showed that the miR-30 family is strongly expressed in podocytes and that its levels vary with disease state. Dysfunction and/or decrease in miRNAs of the miR-30 family could lead to podocyte apoptosis and depletion, glomerulosclerosis, and proteinuric renal disease.…”

Section: Discussionmentioning

confidence: 77%

“…We directly screened the distinct expression profile of urinary miRNAs in patients with FSGS-A using a TaqMan Low Density Array, and candidate miRNAs were selected for further analysis. Because previous studies reported that kidneyenriched miRNAs such as the miR-30 (21,22,27) and miR-10 families (28) as well as miRNAs involved in immune responses and inflammation, including miR-155 (29,30) and miR-146a (26,31), have roles in the modulation of renal function, these kidney-specific and immune response-associated miRNAs are also included in the candidate list.…”

Section: Discussionmentioning

confidence: 99%

“…These 27 miRNAs were considered a part of candidates. Moreover, miR-30 family (21,22) and miR-21 (23,24) were conserved expression in the kidneys of various species and are known to be involved in kidney disease. miR-155 (16,25) and miR-146a (25,26) were associated with immune response and their levels were altered in patients with kidney disease.…”

Section: Identification Of Candidate Mirnasmentioning

confidence: 99%

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Evaluation of MicroRNAs miR-196a, miR-30a-5P, and miR-490 as Biomarkers of Disease Activity among Patients with FSGS

Zhang

Chen

et al. 2014

Clinical Journal of the American Society of Nephrology

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Background and objectives This study aimed to identify urinary microRNAs (miRNAs) as biomarkers for FSGS disease activity.Design, setting, participants, & measurements Candidate urinary miRNAs were identified in pooled urine samples from patients with active FSGS (FSGS-A) and FSGS in remission (FSGS-CR), and were then validated using individual samples. Their levels were compared both under different treatment responses in a prospective study of FSGS and in patients with different membranous nephropathy (MN) and diabetic nephropathy (DN) disease activity. The prediction of these miRNAs for treatment responses was further analyzed in both retrospective and prospective cohorts of patients with FSGS.Results All 54 miRNAs were included as candidate biomarkers, including those with high levels in patients with FSGS-A (n=9) under the TaqMan Low Density Array as well as those with conserved expression in kidneys and involved in immune response. TaqMan probe-based quantitative RT-PCR confirmed the higher levels of four miRNAs in patients with FSGS-A in two independent cohorts (n=18 and n=80). Urinary miR-196a, miR-30a-5p, and miR-490 discriminated FSGS-A from FSGS-CR, with an area under the curve of $0.80. After steroid treatment, their levels were lower in steroid-responsive patients with FSGS (all P,0.001), but were unchanged in steroid-resistant patients. The levels of miRNAs were similar between active MN and MN in remission as well as active DN and incipient DN (all P.0.05). Urinary miR-30a-5p marginally predicted the response to steroid treatment in patients with FSGS-A, with an area under the curve of 0.63 (P=0.03). ConclusionsThe levels of urinary miR-196a, miR-30a-5p, and miR-490 are associated with FSGS disease activity.

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Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Identification Of Candidate Mirnasmentioning

confidence: 99%

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Evaluation of MicroRNAs miR-196a, miR-30a-5P, and miR-490 as Biomarkers of Disease Activity among Patients with FSGS

Zhang

Chen

et al. 2014

Clinical Journal of the American Society of Nephrology

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“…Summarized findings show that miR-34a suppresses brain tumor growth by targeting c-Met and Notch and suggest that miR-34a could serve as a potential therapeutic agent for brain tumors (Li et al, 2009). NOTCH1 is also targeted by down-regulated miR-30 which is demonstrated protecting podocytes by targeting NOTCH1 and TP53 and the loss of it facilitates podocyte injury (Wu et al, 2014).…”

Section: Discussionmentioning

confidence: 94%

Systematical Analysis of Cutaneous Squamous Cell Carcinoma Network of microRNAs, Transcription Factors, and Target and Host Genes

Wang

Xu²,

Wang³

2015

Asian Pacific Journal of Cancer Prevention

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Background: MicroRNAs (miRNAs) are small non-coding RNA molecules found in multicellular eukaryotes which are implicated in development of cancer, including cutaneous squamous cell carcinoma (cSCC). Expression is controlled by transcription factors (TFs) that bind to specific DNA sequences, thereby controlling the flow (or transcription) of genetic information from DNA to messenger RNA. Interactions result in biological signal control networks. Materials and Methods: Molecular components involved in cSCC were here assembled at abnormally expressed, related and global levels. Networks at these three levels were constructed with corresponding biological factors in term of interactions between miRNAs and target genes, TFs and miRNAs, and host genes and miRNAs. Up/down regulation or mutation of the factors were considered in the context of the regulation and significant patterns were extracted. Results: Participants of the networks were evaluated based on their expression and regulation of other factors. Sub-networks with two core TFs, TP53 and EIF2C2, as the centers are identified. These share self-adapt feedback regulation in which a mutual restraint exists. Up or down regulation of certain genes and miRNAs are discussed. Some, for example the expression of MMP13, were in line with expectation while others, including FGFR3, need further investigation of their unexpected behavior. Conclusions: The present research suggests that dozens of components, miRNAs, TFs, target genes and host genes included, unite as networks through their regulation to function systematically in human cSCC. Networks built under the currently available sources provide critical signal controlling pathways and frequent patterns. Inappropriate controlling signal flow from abnormal expression of key TFs may push the system into an incontrollable situation and therefore contributes to cSCC development.

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“…Different miRs have been found to be enriched in human kidneys include miR-192, miR-194, miR-204, miR-215 and miR-216 [11]. MiRs are also essential for podocyte homeostasis [12][13][14][15] and can be secreted in body fluids [16,17].…”

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confidence: 99%

The Zebrafish Model to Study the Role of microRNAs in Glomerular Function and Disease

Müller-Deile¹,

Schiffer²

2017

Adv Tech Biol Med

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The zebrafish physiology of many organs including the kidney is very similar to that of human beings. Zebrafish develop from a fertilized egg to free-swimming larvae in only 48 h. The zebrafish larvae's correlate for the human kidney is the pronephros consisting of two nephrons with glomeruli fused at the embryo mid-line ventral to the dorsal aorta [1] ( Figure 1a).The glomerular filtration barrier of the pronephros is ultrastructurally almost indistinguishable from a mammalian glomerulus with interdigitating podocyte foot processes, a thin glomerular basement membrane and a fenestrated glomerular endothelium [2]. These structures can be found in 120 h old zebrafish larvae on ultrastructural level (Figures 1b and 1c). To generate these pictures zebrafish larvae were fixed in solution D and embedded in EPON. Ultrathin sectioning from head to tail was performed with a microtome until the glomerular region was found and sections transferred onto copper slit grids that were stained with uranyl acetate and lead citrate. Imaging was done with a transmission electron microscope.The pronephros tubular epithelium is composed of two proximal tubule segments, a proximal straight tubule as well as the early and late distal tubus [3]. The tubular system expresses a brush border of microvilli on the apical side for reabsorption processes (Figure 1d). The glomerular filtration of the zebrafish pronephros begins around 48 h post fertilization (hpf) [4]. Taking into consideration the structural and functional similarities and the fact that zebrafish gene expression can easily be influenced by specific knockdown and overexpression techniques using microinjections of morpholinos (MOs), mRNAs, microRNAs (miRs), small RNAs or CRISPR/Cas9 technology, the zebrafish serves as an ideal model to study glomerular diseases [5]. We and others successfully used the zebrafish model to screen for novel genes involved in kidney diseases [6][7][8]. On the other hand, gene mutations identified from human genetic studies can be verified as causative factors of proteinuric kidney disease in the zebrafish model. An upcoming field of research interest is the role of miRs in disease processes. MiRs regulate gene expression posttranscriptional by binding to the 3'-untranslated region (3' UTR) of a target mRNA and inhibiting translation [9,10]. Different miRs have been found to be enriched in human kidneys include miR-192, miR-194, miR-204, miR-215 and miR-216 [11]. MiRs are also essential for podocyte homeostasis [12][13][14][15] and can be secreted in body fluids [16,17].To antagonize the function of miRs, several antagomirs have been engineered and are commercially available. On the contrary, miR effects can be enhanced with miR mimics, which are chemically modified short double-stranded RNA sequences.Delivery of miRs in the zebrafish larvae system can be accomplished by microinjection of miR mimics in one-to-four cell stage or at 48 hpf by cardinal vein (c.v.) injection. After injections in egg stage the miR mimic is equally distributed in all zebra...

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Downregulation of MicroRNA-30 Facilitates Podocyte Injury and Is Prevented by Glucocorticoids

Cited by 155 publications

References 43 publications

Evaluation of MicroRNAs miR-196a, miR-30a-5P, and miR-490 as Biomarkers of Disease Activity among Patients with FSGS

Evaluation of MicroRNAs miR-196a, miR-30a-5P, and miR-490 as Biomarkers of Disease Activity among Patients with FSGS

Systematical Analysis of Cutaneous Squamous Cell Carcinoma Network of microRNAs, Transcription Factors, and Target and Host Genes

The Zebrafish Model to Study the Role of microRNAs in Glomerular Function and Disease

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