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Article: Renal stromal miRNAs are required for normal nephrogenesis and glomerular mesangial survival

TitleRenal stromal miRNAs are required for normal nephrogenesis and glomerular mesangial survival
Authors
Issue Date2015
PublisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)2051-817X
Citation
Physiological Reports, 2015, v. 3 n. 10, p. article no. e12537 How to Cite?
AbstractMicroRNAs are small noncoding RNAs that post-transcriptionally regulate mRNA levels. While previous studies have demonstrated that miRNAs are indispensable in the nephron progenitor and ureteric bud lineage, little is understood about stromal miRNAs during kidney development. The renal stroma (marked by expression of FoxD1) gives rise to the renal interstitium, a subset of peritubular capillaries, and multiple supportive vascular cell types including pericytes and the glomerular mesangium. In this study, we generated FoxD1(GC);Dicer(fl/fl) transgenic mice that lack miRNA biogenesis in the FoxD1 lineage. Loss of Dicer activity resulted in multifaceted renal anomalies including perturbed nephrogenesis, expansion of nephron progenitors, decreased renin-expressing cells, fewer smooth muscle afferent arterioles, and progressive mesangial cell loss in mature glomeruli. Although the initial lineage specification of FoxD1(+) stroma was not perturbed, both the glomerular mesangium and renal interstitium exhibited ectopic apoptosis, which was associated with increased expression of Bcl2l11 (Bim) and p53 effector genes (Bax, Trp53inp1, Jun, Cdkn1a, Mmp2, and Arid3a). Using a combination of high-throughput miRNA profiling of the FoxD1(+)-derived cells and mRNA profiling of differentially expressed transcripts in FoxD1(GC);Dicer(fl/fl) kidneys, at least 72 miRNA:mRNA target interactions were identified to be suppressive of the apoptotic program. Together, the results support an indispensable role for stromal miRNAs in the regulation of apoptosis during kidney development.
Persistent Identifierhttp://hdl.handle.net/10722/232046
ISSN
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorChu, JYS-
dc.contributor.authorPhua, YL-
dc.contributor.authorMarrone, AK-
dc.contributor.authorBodnar, AJ-
dc.contributor.authorSims-Lucas, S-
dc.contributor.authorHo, J-
dc.date.accessioned2016-09-20T05:27:19Z-
dc.date.available2016-09-20T05:27:19Z-
dc.date.issued2015-
dc.identifier.citationPhysiological Reports, 2015, v. 3 n. 10, p. article no. e12537-
dc.identifier.issn2051-817X-
dc.identifier.urihttp://hdl.handle.net/10722/232046-
dc.description.abstractMicroRNAs are small noncoding RNAs that post-transcriptionally regulate mRNA levels. While previous studies have demonstrated that miRNAs are indispensable in the nephron progenitor and ureteric bud lineage, little is understood about stromal miRNAs during kidney development. The renal stroma (marked by expression of FoxD1) gives rise to the renal interstitium, a subset of peritubular capillaries, and multiple supportive vascular cell types including pericytes and the glomerular mesangium. In this study, we generated FoxD1(GC);Dicer(fl/fl) transgenic mice that lack miRNA biogenesis in the FoxD1 lineage. Loss of Dicer activity resulted in multifaceted renal anomalies including perturbed nephrogenesis, expansion of nephron progenitors, decreased renin-expressing cells, fewer smooth muscle afferent arterioles, and progressive mesangial cell loss in mature glomeruli. Although the initial lineage specification of FoxD1(+) stroma was not perturbed, both the glomerular mesangium and renal interstitium exhibited ectopic apoptosis, which was associated with increased expression of Bcl2l11 (Bim) and p53 effector genes (Bax, Trp53inp1, Jun, Cdkn1a, Mmp2, and Arid3a). Using a combination of high-throughput miRNA profiling of the FoxD1(+)-derived cells and mRNA profiling of differentially expressed transcripts in FoxD1(GC);Dicer(fl/fl) kidneys, at least 72 miRNA:mRNA target interactions were identified to be suppressive of the apoptotic program. Together, the results support an indispensable role for stromal miRNAs in the regulation of apoptosis during kidney development.-
dc.languageeng-
dc.publisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)2051-817X-
dc.relation.ispartofPhysiological Reports-
dc.rightsPhysiological Reports. Copyright © John Wiley & Sons Ltd.-
dc.rightsPreprint: This is the pre-peer reviewed version of the following article: [FULL CITE], which has been published in final form at [Link to final article using the DOI]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. Postprint: This is the peer reviewed version of the following article: [FULL CITE], which has been published in final form at [Link to final article using the DOI]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. Special Statement for Preprint only Before publication: 'This is a preprint of an article accepted for publication in [The Journal of Pathology] Copyright © ([year]) ([Pathological Society of Great Britain and Ireland])'. After publication: the preprint notice should be amended to follows: 'This is a preprint of an article published in [include the complete citation information for the final version of the Contribution as published in the print edition of the Journal]' For Cochrane Library/ Cochrane Database of Systematic Reviews, add statement & acknowledgement : ‘This review is published as a Cochrane Review in the Cochrane Database of Systematic Reviews 20XX, Issue X. Cochrane Reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and the Cochrane Database of Systematic Reviews should be consulted for the most recent version of the Review.’ Please include reference to the Review and hyperlink to the original version using the following format e.g. Authors. Title of Review. Cochrane Database of Systematic Reviews 20XX, Issue #. Art. No.: CD00XXXX. DOI: 10.1002/14651858.CD00XXXX (insert persistent link to the article by using the URL: http://dx.doi.org/10.1002/14651858.CD00XXXX) (This statement should refer to the most recent issue of the Cochrane Database of Systematic Reviews in which the Review published.)-
dc.titleRenal stromal miRNAs are required for normal nephrogenesis and glomerular mesangial survival-
dc.typeArticle-
dc.identifier.emailChu, JYS: jyschu@hku.hk-
dc.identifier.authorityChu, JYS=rp00684-
dc.identifier.doi10.14814/phy2.12537-
dc.identifier.pmcidPMC4632944-
dc.identifier.hkuros265029-
dc.identifier.volume3-
dc.identifier.issue10-
dc.identifier.spagearticle no. e12537-
dc.identifier.epagearticle no. e12537-
dc.publisher.placeUnited Kingdom-

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