miR181c promotes apoptosis and suppresses proliferation of metanephric mesenchyme cells by targeting <i>Six2 in vitro</i>

Lv, Xiaoyan; Mao, Zhizhong; Lyu, Zhong-Shi; Zhang, Pengzong; Zhan, Alan; Wang, Jian; Yang, Hui; Li, Mi; Wang, Honglian; Wan, Qianya; Wei, Hongyuan; Wang, Ming; Wang, Nian; Li, Xun; Liu, Yi; Zhao, Hui; Zhou, Qin

doi:10.1002/cbf.3052

Cited by 16 publications

(17 citation statements)

References 24 publications

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“…Li and colleagues, in an acute lung injury model, have shown that overexpressed miR-181a is related to decreased Bcl2 protein level; conversely, the inhibition of miR-181a increase Bcl2 levels (Li et al, 2016). The current study confirming Lv et al (2014) demonstrated that miR-181c regulates negatively, the expression of Six2 expression and cell proliferation, in parallel to the loss of mesenchymal cells phenotype during kidney development in LP 17-DG offspring.…”

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confidence: 75%

“…In the kidney ontogenic context, several researchers have demonstrated that miRNAs are indispensable for nephron development (Chu et al, 2014;Harvey et al, 2008;Lv et al, 2014;. Prior studies have shown that during kidney development, the underexpression of miRNAs in MM progenitor cells results in a premature reduction of cell proliferation and, consequently, decreased the number of nephrons (Ho et al, 2011;Nagalakshmi et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

“…However, many regulatory factors and signaling pathways involved in renal ontogenesis maintain unclear (Wang et al, 2018). It is known that miRNAs play a crucial role in regulating gene expression during the renal developmental processes (Lv et al, 2014;Phua et al, 2015b;Wei et al, 2014). So far, to our knowledge, no prior study has performed an integrative miRNA and mRNA expression profiling analysis in maternal low-protein intake 17-DG male metanephros.…”

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confidence: 99%

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Impact of gestational low-protein intake on embryonic kidney microRNA expression and in the nephron progenitor cells of the male offspring fetus

Gontijo

Sene

Bôer³

et al. 2020

Preprint

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Authors have demonstrated that gestational low-protein (LP) intake offspring showed a lower birth weight, reduced nephrons numbers and renal salt excretion, chronic renal failure, and arterial hypertension development when compared to normal (NP) protein intake group in adult life. The current study was aimed to evaluate the miRNAs and predicted gene expression patterns in the fetal kidney at 17 days of gestational (17-DG) protein-restricted male offspring (LP) in an attempt to elucidate the possible molecular pathways and disorders involved in renal cell proliferation and differentiation during kidney development. By NGS and RT-qPCR were identified, 44 differentially expressed miRNAs, which 19 miRNA were up-and 25 downregulated in LP compared to NP offspring metanephros. Among the top 10 deregulated miRNAs, the study selected 7 miRNAs which its biological targets were related to proliferation, differentiation, and cellular apoptosis processes. As could be seen below, both miRNA-Seq and TaqMan data analysis have shown a consistent change of miRNA expression in LP animals relative to control NP age-matched animals. By immunofluorescence, the LP fetus showed a significant 28% reduction of Six-2 labeled cells when compared to NP offspring associated with a reduced percentage of cell number and c-Myc metanephogenic cap and ureter bud immunostained cells in LP relative to NP offspring. 4 Additionally, the Ki-67 labeled area in CM was 48% lesser in LP compared to NP age-matched fetus. On the other hand, in LP, the CM and UB β-catenin marked area were 154 and 85% raised, respectively. Mtor immunoreactivity was also significantly higher in LP CM (139%) and UB (104%) compared to the NP fetus. In the LP offspring, the TGFβ-1 in UBs cells staining increased (about 30%). In contrast, Zeb1 metanephrosstained, located in the CM nuclei cells, enhanced 30% in LP and Zeb2 immunofluorescence, although present in whole metanephros structures, was similar in both experimental groups. In conclusion, the present study demonstrates that the miRNAs, mRNAs, and proteins are modified in LP animals with 17 DGs leading to the reduction of the reciprocal induction between CM and UB, and hence the number of nephrons. These findings will facilitate new functional approaches and further studies to elucidate the regulatory mechanisms involved in the processes of proliferation, differentiation, and apoptosis that occurs during renal development.

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confidence: 75%

Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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Impact of gestational low-protein intake on embryonic kidney microRNA expression and in the nephron progenitor cells of the male offspring fetus

Gontijo

Sene

Bôer³

et al. 2020

Preprint

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“…These research studies implied that the research of the upstream regulatory factor towards Six2 is of great importance. According to the limited associated reports, the miR181 family is able directly target the 3′UTR of Six2 and suppress its expression [18,19], Recombination signal binding protein for immunoglobulin kappa J region (Rbpj) is sufficient for the down-regulation of Six2 [20], Notch2 can shut down the Six2 mediated program for progenitor maintenance [21], and Pax2/Eya1/Hox11 complex binds to the proximal promoter of Six2 and thus regulates its expression [22]. …”

Section: Discussionmentioning

confidence: 99%

TβRII Regulates the Proliferation of Metanephric Mesenchyme Cells through Six2 In Vitro

Mao

Lyu

Huang

et al. 2017

IJMS

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The transforming growth factor-β (TGFβ) family signaling pathways play an important role in regulatory cellular networks and exert specific effects on developmental programs during embryo development. However, the function of TGFβ signaling pathways on the early kidney development remains unclear. In this work, we aim to detect the underlying role of TGFβ type II receptor (TβRII) in vitro, which has a similar expression pattern as the crucial regulator Six2 during early kidney development. Firstly, the 5-ethynyl-2′-deoxyuridine (EdU) assay showed knock down of TβRII significantly decreased the proliferation ratio of metanephric mesenchyme (MM) cells. Additionally, real-time Polymerase Chain Reaction (PCR) and Western blot together with immunofluorescence determined that the mRNA and protein levels of Six2 declined after TβRII knock down. Also, Six2 was observed to be able to partially rescue the proliferation phenotype caused by the depletion of TβRII. Moreover, bioinformatics analysis and luciferase assay indicated Smad3 could transcriptionally target Six2. Further, the EdU assay showed that Smad3 could also rescue the inhibition of proliferation caused by the knock down of TβRII. Taken together, these findings delineate the important function of the TGFβ signaling pathway in the early development of kidney and TβRII was shown to be able to promote the expression of Six2 through Smad3 mediating transcriptional regulation and in turn activate the proliferation of MM cells.

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Section: Introductionmentioning

confidence: 99%

Impact of gestational low-protein intake on embryonic kidney microRNA expression and in the nephron progenitor cells of the male offspring fetus

Sene

Scarano

Zapparoli

et al. 2020

Preprint

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Background: Authors demonstrated that gestational low-protein (LP) intake offspring presents a lower birthweight, reduced nephrons numbers and renal salt excretion, arterial hypertension and renal failure development when compared to normal protein (NP) intake rats in adulthood. The current study evaluated the miRNAs and predicted gene expression patterns in the 17-days LP (17-DG) fetal kidney to elucidate the molecular pathways and renal cell proliferation and differentiation profile. Methods: Pregnant Wistar rats were allocated into two groups, according to protein supply during pregnancy: NP (normal protein diet- 17%) or LP (low protein diet-6%). miRNA transcriptome sequencing (miRNA-Seq) was performed on the MiSeq platform and, RT-qPCR of predicted target genes, immunohistochemistry and morphological quantification from 17-DG offspring kidneys using previously described methods. Results: Forty-four expressed miRNAs, which 19 miRNA were up- and 25 downregulated, were identified in 17-DG LP fetuses compared to age-matched NP offspring. The study selected 7 miRNAs related to proliferation, differentiation, and cellular apoptosis processes. The study showed a reduced cell number, Six-2 and c-Myc immunoreactivity in metanephros cap (CM) and ureter bud (UB) in 17-DG LP fetuses. Also, Ki-67 immunoreactivity in CM was 48% lesser in LP compared to NP age-matched fetus. Conversely, in LP CM and UB β-catenin was 154% and 85% markedly enhanced, respectively and, mTOR immunoreactivity was also higher in LP CM (139%) and UB (104%) compared to the NP offspring. UB TGFβ-1 staining cells increased (about 30%) in the LP offspring. Otherwise, Zeb1 metanephros-stained, enhanced 30% in LP offspring without Zeb2 staining in both groups. Conclusions: The present study demonstrates that maternal protein restriction change miRNAs, mRNAs, and critical proteins expression involved in the processes of proliferation, differentiation, and apoptosis that occurs during renal development. The renal ontogenic dysfunction caused by maternal protein restriction promotes a reduced reciprocal interaction between CM and UB, and consequently, a programmed and expressive decrease in the nephron number fetuses.

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miR181c promotes apoptosis and suppresses proliferation of metanephric mesenchyme cells by targeting Six2 in vitro

Cited by 16 publications

References 24 publications

Impact of gestational low-protein intake on embryonic kidney microRNA expression and in the nephron progenitor cells of the male offspring fetus

Impact of gestational low-protein intake on embryonic kidney microRNA expression and in the nephron progenitor cells of the male offspring fetus

TβRII Regulates the Proliferation of Metanephric Mesenchyme Cells through Six2 In Vitro

Impact of gestational low-protein intake on embryonic kidney microRNA expression and in the nephron progenitor cells of the male offspring fetus

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