MicroRNAs in HIV-associated nephropathy (HIVAN)

Cheng, Kang; Rai, Partab; Plagov, Andrei; Lan, Xiqian; Subrati, Ashaan; Husain, Mohammad; Malhotra, Ashwani; Singhal, Pravin C.

doi:10.1016/j.yexmp.2012.10.011

Cited by 14 publications

(13 citation statements)

References 52 publications

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“…The replication defective HIV-1 virus stocks were obtained by cotransfected pNL4-3:ΔG/P-GFP construct and packaging constructs pCMV R8.91 and pMD.G plasmids into 293 T cells as previously described [5]. Briefly, pNL4-3:ΔG/P-GFP construct was produced by reconstruction of pNL4-3 clone, the same proviral construct used to generate Tg26 transgenic mice, by substituting gag/pol genes with GFP reporter gene.…”

Section: Methodsmentioning

confidence: 99%

“…Profiles of miRNAs expression in kidney diseases, i.e., polycystic kidney disease [26], diabetic nephropathy [18], ischemia reperfusion injury [9], renal cancer [10], hypertensive nephrosclerosis [37] and kidney fibrosis [6,38] have been investigated. Recently, we reported the profile of miRNAs expression in HIV-1 transgenic mice (Tg26) [5], the most frequently used mouse model of HIV-associated nephropathy (HIVAN) [15]. This report suggested that miRNAs had potential to play a role in the pathogenesis of HIVAN.…”

Section: Introductionmentioning

confidence: 99%

“…We recently reported the miRNAs’ expression, including miR-200 family, were down regulated in HIVAN mice and HIV-transduced podocytes [5]. MiR-200 has been revealed to inhibit EMT in cancer cells as well as in renal tubular cells by targeting Zeb1 and Zeb2, the negative transcription factors of E-cadherin [11,27].…”

Section: Introductionmentioning

confidence: 99%

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Rapamycin-induced modulation of miRNA expression is associated with amelioration of HIV-associated nephropathy (HIVAN)

Cheng¹,

Rai²,

Plagov³

et al. 2013

Experimental Cell Research

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Recent studies suggested that miRNAs are involved in the development of the pathogenesis of HIV-associated nephropathy (HIVAN). Rapamycin, a widely used mTOR inhibitor, has been demonstrated to slow down the progression of HIVAN. However, the role of miRNA in the regulation of these processes has not been investigated so far. In the current study, we have used a microarray-based approach in combination with real-time PCR to profile the miRNA expression patterns in rapamycin-treated HIVAN mice (Tg26). Our results demonstrated that 19 miRNAs belonging to 13 different families expressed differentially in renal tissues of rapamycin-receiving Tg26 mice when compared to Tg26 mice-receiving saline only. The patterns of miRNAs expression in rapamycin-receiving Tg26 mice took a reverse turn. These miRNAs were classified into 8 functional categories. In in vitro studies, we examined the expression of specific miRNAs in HIV-1 transduced human podocytes (HIV/HPs). HIV/HPs displayed attenuation of expression of miR-99a, -100a, -199a and miR-200, whereas, rapamycin inhibited this effect of HIV. These findings suggest that rapamycin-mediated up-regulation of specific miRNAs could contribute to amelioration of renal lesions in HIVAN mice.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Rapamycin-induced modulation of miRNA expression is associated with amelioration of HIV-associated nephropathy (HIVAN)

Cheng¹,

Rai²,

Plagov³

et al. 2013

Experimental Cell Research

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“…In mice, many C2MC miRNAs were identified to be the major components in the dynamic regulatory network during embryonic development [39], skeletal and cardiac muscle differentiation or function [9,36], angiogenesis [3] and lung development [37]. Studies have also shown that many C2MC miRNAs or their relatives were often among the most significantly-altered miRNAs in responses to multiple types of cellular stresses, which included nutrition deprivation [11], hyperglycemia [3,38], hypertonic stress [16], oxidative stress [43], xenobiotic stress [41], aging [48], cigarette smoke [17,18], septic shock [40] and virus infection [7,28]. Although there were studies showing that a few C2MC miRNAs might act as important ribo-regulators in the control of cell fate decision, cell proliferation, immune responses, cell cycle and apoptosis [9,11,27,32,37,39,49], the exact roles of many more C2MC miRNAs in cellular stress responses and other biological processes were unknown and remained to be further explored.…”

Section: Discussionmentioning

confidence: 99%

Sfmbt2 10th intron-hosted miR-466(a/e)-3p are important epigenetic regulators of Nfat5 signaling, osmoregulation and urine concentration in mice

Luo

Liu

et al. 2014

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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Sfmbt2-hosted miR-466a-3p and its close relatives are often among the most significantly up-regulated or down-regulated miRNAs in responses to numerous deleterious environmental stimuli. The exact roles of these miRNAs in cellular stress responses, however, are not clear. Here we showed that many Sfmbt2-hosted miRNAs were highly hypertonic stress responsive in vitro and in vivo. In renal medulla, water deprivation induced alterations in the expression of miR-466(a/b/c/e/p)-3p in a pattern similar to that of miR-200b-3p, a known regulator of osmoresponsive transcription factor Nfat5. Remarkably, exposure of mIMCD3 cells to an arginine vasopressin analog time-dependently down-regulated the expression of miR-466(a/b/c/e/p)-3p and miR-200b-3p, which provides a novel regulatory mechanism for these osmoresponsive miRNAs. In cultured mIMCD3 cells we further demonstrated that miR-466a-3p and miR-466g were capable of targeting Nfat5 by interacting with its 3'UTR. In transgenic mice overexpressing miR-466a-3p, significant down-regulation of Nfat5 and many other osmoregulation-related genes was observed in both the renal cortex and medulla. Moreover, sustained transgenic over-expression of miR-466a-3p was found to be associated with polydipsia, polyuria and disturbed ion homeostasis and kidney morphology. Since the mature sequence of miR-466a-3p is completely equivalent to that of miR-466e-3p and that the seed sequence of miR-466a-3p is completely equivalent to that of miR-297(a/b/c)-3p, miR-466d-3p, miR-467g and miR-669d-3p, and that miR-466a-3p differs from miR-466(b/c/p)-3p only in a 5' nucleotide, we propose that miR-466a-3p and many of its close relatives are important epigenetic regulators of renal Nfat5 signaling, osmoregulation and urine concentration in mice.

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“…These mice expressed HIV-1 genes abundantly in skin, muscle, tail, and variably in kidneys, intestine, and thymus [30]. The Tg26 mouse line has been widely used as a model of HIV-1-associated nephropathy [31]. However, whether bone marrow cells in Tg26 mice expressed HIV-1 had not previously been investigated.…”

Section: Discussionmentioning

confidence: 99%

Bone-derived mesenchymal stromal cells from HIV transgenic mice exhibit altered proliferation, differentiation capacity and paracrine functions along with impaired therapeutic potential in kidney injury

Cheng

Rai

Lan

et al. 2013

Experimental Cell Research

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Mesenchymal stem cells (MSCs) secrete paracrine factors that could be cytoprotective and serve roles in immunoregulation during tissue injury. Although MSCs express HIV receptors, and co-receptors, and are susceptible to HIV infection, whether HIV-1 may affect biological properties of MSCs needs more study. We evaluated cellular proliferation, differentiation and paracrine functions of MSCs isolated from compact bones of healthy control mice and Tg26 HIV-1 transgenic mice. The ability of MSCs to protect against cisplatin toxicity was studied in cultured renal tubular cells as well as in intact mice. We successfully isolated MSCs from healthy mice and Tg26 HIV-1 transgenic mice and found the latter expressed viral Nef, Vpu, NL4-3 and Vif genes. The proliferation and differentiation of Tg26 HIV-1 MSCs was inferior to MSCs from healthy mice. Moreover, transplantation of Tg26 HIV-1 MSCs less effectively improved outcomes compared with healthy MSCs in mice with acute kidney injury. Also, Tg26 HIV-1 MSCs secreted multiple cytokines, but at significantly lower levels than healthy MSCs, which resulted in failure of conditioned medium from these MSCs to protect cultured renal tubular cells from cisplatin toxicity. Therefore, HIV-1 had adverse biological effects on MSCs extending to their proliferation, differentiation, function, and therapeutic potential. These findings will help in advancing mechanistical insight in renal injury and repair in the setting of HIV-1 infection.

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MicroRNAs in HIV-associated nephropathy (HIVAN)

Cited by 14 publications

References 52 publications

Rapamycin-induced modulation of miRNA expression is associated with amelioration of HIV-associated nephropathy (HIVAN)

Rapamycin-induced modulation of miRNA expression is associated with amelioration of HIV-associated nephropathy (HIVAN)

Sfmbt2 10th intron-hosted miR-466(a/e)-3p are important epigenetic regulators of Nfat5 signaling, osmoregulation and urine concentration in mice

Bone-derived mesenchymal stromal cells from HIV transgenic mice exhibit altered proliferation, differentiation capacity and paracrine functions along with impaired therapeutic potential in kidney injury

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