Intrarenal expression of microRNAs in patients with IgA nephropathy

Wang, Gang; Kwan, Bonnie Ching‐Ha; Lai, Fernand M.M.; Choi, Pui–Wah; Chow, Kai‐Ming; Li, Philip K.T.; Szeto, Cheuk‐Chun

doi:10.1038/labinvest.2009.118

Cited by 105 publications

(77 citation statements)

References 25 publications

(25 reference statements)

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“…Furthermore, recent studies suggest a similar relationship in the kidney in which miR-29b is reduced in a model of hypertensive renal disease in the kidneys of salt-sensitive rats. 30 Although the evidence suggesting a role for miRNAs in renal pathophysiology has been rapidly increasing, 10,12,13,[31][32][33][34] the effect of known nephroprotective treatments on the expression of miRNAs, or their possible contribution as protective agents against renal fibrosis, has yet to be established. In this context, we also evaluated miR-29 expression in diabetic UNx rats treated with the ROCK inhibitor fasudil or ARB losartan.…”

Section: Discussionmentioning

confidence: 99%

Suppression of microRNA-29 Expression by TGF-β1 Promotes Collagen Expression and Renal Fibrosis

Wang

Komers

Carew

et al. 2012

Journal of the American Society of Nephrology

446

333

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Synthesis and deposition of extracellular matrix (ECM) within the glomerulus and interstitium characterizes renal fibrosis, but the mechanisms underlying this process are incompletely understood. The profibrotic cytokine TGF-b1 modulates the expression of certain microRNAs (miRNAs), suggesting that miRNAs may have a role in the pathogenesis of renal fibrosis. Here, we exposed proximal tubular cells, primary mesangial cells, and podocytes to TGF-b1 to examine its effect on miRNAs and subsequent collagen synthesis. TGF-b1 reduced expression of the miR-29a/b/c/family, which targets collagen gene expression, and increased expression of ECM proteins. In both resting and TGF-b1-treated cells, ectopic expression of miR-29 repressed the expression of collagens I and IV at both the mRNA and protein levels by targeting the 39untranslated region of these genes. Furthermore, we observed low levels of miR-29 in three models of renal fibrosis representing early and advanced stages of disease. Administration of the Rho-associated kinase inhibitor fasudil prevented renal fibrosis and restored expression of miR-29. Taken together, these data suggest that TGF-b1 inhibits expression of the miR-29 family, thereby promoting expression of ECM components. Pharmacologic modulation of these miRNAs may have therapeutic potential for progressive renal fibrosis.

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Section: Discussionmentioning

confidence: 99%

Suppression of microRNA-29 Expression by TGF-β1 Promotes Collagen Expression and Renal Fibrosis

Wang

Komers

Carew

et al. 2012

Journal of the American Society of Nephrology

446

333

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“…[28][29][30] However, miRNAs potentially involved in the pathogenesis of IgAN have been partially studied in renal tissue. 31 Starting from a microarray miRNA expression profile in PBMCs of patients with IgAN and using several bioinformatic approaches, we identified 37 miRNAs that are differentially regulated in IgAN patients compared with healthy persons, along with their candidate target genes.…”

Section: Discussionmentioning

confidence: 99%

Abnormal miR-148b Expression Promotes Aberrant Glycosylation of IgA1 in IgA Nephropathy

Serino

Sallustio²,

Cox³

et al. 2012

Journal of the American Society of Nephrology

186

166

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“…Mature miRs are short noncoding RNAs that bind to (partially) complementary sequences, most commonly found in the 3=UTR (untranslated region) of target mRNAs, which results in inhibition of protein synthesis by degradation or translational repression of the target mRNA. miRs play a role in endothelial biology (29,38) and also have been associated with pathogenesis and the progression of various kidney diseases (16,31,37,39). Harris et al (10) and more recently Salvucci et al (26) demonstrated a link between miR expression in endothelial cells and inflammation by showing that high miR-126 levels related to low VCAM-1 protein expression in human umbilical vein endothelial cells (HUVEC) in vitro.…”

mentioning

confidence: 99%

MicroRNA-126 contributes to renal microvascular heterogeneity of VCAM-1 protein expression in acute inflammation

Ásgeirsdóttir

Solingen

Kurniati

et al. 2012

American Journal of Physiology-Renal Physiology

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Endothelial cells in different microvascular segments of the kidney have diverse functions and exhibit differential responsiveness to disease stimuli. The responsible molecular mechanisms are largely unknown. We previously showed that during hemorrhagic shock, VCAM-1 protein was expressed primarily in extraglomerular compartments of the kidney, while E-selectin protein was highly induced in glomeruli only (van Meurs M, Wulfert FM, Knol AJ, de Haes A, Houwertjes M, Aarts LPHJ, Molema G. Shock 29: 291–299, 2008). Here, we investigated the molecular control of expression of these endothelial cell adhesion molecules in mouse models of renal inflammation. Microvascular segment-specific responses to the induction of anti-glomerular basement membrane (anti-GBM), glomerulonephritis and systemic TNF-α treatment showed that E-selectin expression was transcriptionally regulated, with high E-selectin mRNA and protein levels preferentially expressed in the glomerular compartment. In contrast, VCAM-1 mRNA expression was increased in both arterioles and glomeruli, while VCAM-1 protein expression was limited in the glomeruli. These high VCAM-1 mRNA/low VCAM-1 protein levels were accompanied by high local microRNA (miR)-126 and Egfl7 levels, as well as higher Ets1 levels compared with arteriolar expression levels. Using miR-reporter constructs, the functional activity of miR-126 in glomerular endothelial cells could be demonstrated. Moreover, in vivo knockdown of miR-126 function unleashed VCAM-1 protein expression in the glomeruli upon inflammatory challenge. These data imply that miR-126 has a major role in the segmental, heterogenic response of renal microvascular endothelial cells to systemic inflammatory stimuli.

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Intrarenal expression of microRNAs in patients with IgA nephropathy

Cited by 105 publications

References 25 publications

Suppression of microRNA-29 Expression by TGF-β1 Promotes Collagen Expression and Renal Fibrosis

Suppression of microRNA-29 Expression by TGF-β1 Promotes Collagen Expression and Renal Fibrosis

Abnormal miR-148b Expression Promotes Aberrant Glycosylation of IgA1 in IgA Nephropathy

MicroRNA-126 contributes to renal microvascular heterogeneity of VCAM-1 protein expression in acute inflammation

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