C-reactive protein promotes acute renal inflammation and fibrosis in unilateral ureteral obstructive nephropathy in mice

Li, Z I; Chung, Arthur Chi Kong; Zhou, Li; Huang, Xiao Ru; Liu, Fei; Fu, Ping; Fan, Junming; Szalai, Alexander J.; Lan, Hui‐Yao

doi:10.1038/labinvest.2011.42

Cited by 65 publications

(70 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, our results support previous findings that hsa-miR-29b is a key downregulator of Wnt antagonists like Dkk1, Kremen2, sFRP2, and WIF1 . The data also show a positive correlation of hsa-miR-29b with Wnt1, one of the activators of canonical Wnt signaling pathway and β-catenin which activates target gene transcription (Li et al 2011). Correlation between miRNA fold-change values and global mRNA-expression levels in HOBs from 95 individuals.…”

Section: Discussionmentioning

confidence: 71%

Global miRNA expression and correlation with mRNA levels in primary human bone cells

Laxman

Rubin

Mallmin

et al. 2015

RNA

View full text Add to dashboard Cite

MicroRNAs (miRNAs) are important post-transcriptional regulators that have recently introduced an additional level of intricacy to our understanding of gene regulation. The aim of this study was to investigate miRNA-mRNA interactions that may be relevant for bone metabolism by assessing correlations and interindividual variability in miRNA levels as well as global correlations between miRNA and mRNA levels in a large cohort of primary human osteoblasts (HOBs) obtained during orthopedic surgery in otherwise healthy individuals. We identified differential expression (DE) of 24 miRNAs, and found 9 miRNAs exhibiting DE between males and females. We identified hsa-miR-29b, hsa-miR-30c2, and hsa-miR-125b and their target genes as important modulators of bone metabolism. Further, we used an integrated analysis of global miRNA-mRNA correlations, mRNAexpression profiling, DE, bioinformatics analysis, and functional studies to identify novel target genes for miRNAs with the potential to regulate osteoblast differentiation and extracellular matrix production. Functional studies by overexpression and knockdown of miRNAs showed that, the differentially expressed miRNAs hsa-miR-29b, hsa-miR-30c2, and hsa-miR-125b target genes highly relevant to bone metabolism, e.g., collagen, type I, α1 (COL1A1), osteonectin (SPARC), Runt-related transcription factor 2 (RUNX2), osteocalcin (BGLAP), and frizzled-related protein (FRZB). These miRNAs orchestrate the activities of key regulators of osteoblast differentiation and extracellular matrix proteins by their convergent action on target genes and pathways to control the skeletal gene expression.

show abstract

Section: Discussionmentioning

confidence: 71%

Global miRNA expression and correlation with mRNA levels in primary human bone cells

Laxman

Rubin

Mallmin

et al. 2015

RNA

View full text Add to dashboard Cite

show abstract

“…In mice, overexpression of CRP strongly potentiates inflammation and fibrosis [26–29]. PTX3 is associated with inflammation in humans, but in mice appears to be pro-inflammatory in some models and limits inflammation in other models [30,31].…”

Section: Introductionmentioning

confidence: 99%

The Long Pentraxin PTX3 Promotes Fibrocyte Differentiation

et al. 2015

View full text Add to dashboard Cite

Monocyte-derived, fibroblast-like cells called fibrocytes are associated with fibrotic lesions. The plasma protein serum amyloid P component (SAP; also known as pentraxin-2, PTX2) inhibits fibrocyte differentiation in vitro, and injections of SAP inhibit fibrosis in vivo. SAP is a member of the pentraxin family of proteins that includes C-reactive protein (CRP; PTX1) and pentraxin-3 (PTX3). All three pentraxins are associated with fibrosis, but only SAP and CRP have been studied for their effects on fibrocyte differentiation. We find that compared to SAP and CRP, PTX3 promotes human and murine fibrocyte differentiation. The effect of PTX3 is dependent on FcγRI. In competition studies, the fibrocyte-inhibitory activity of SAP is dominant over PTX3. Binding competition studies indicate that SAP and PTX3 bind human FcγRI at different sites. In murine models of lung fibrosis, PTX3 is present in fibrotic areas, and the PTX3 distribution is associated with collagen deposition. In lung tissue from pulmonary fibrosis patients, PTX3 has a widespread distribution, both in unaffected tissue and in fibrotic lesions, whereas SAP is restricted to areas adjacent to vessels, and absent from fibrotic areas. These data suggest that the relative levels of SAP and PTX3 present at sites of fibrosis may have a significant effect on the ability of monocytes to differentiate into fibrocytes.

show abstract

“…In the context of renal transplantation, elevated CRP levels in graft recipients associate with graft failure, and local expression of CRP mRNA in donated kidneys correlates with both acute and chronic rejection (14,31,43). There is evidence from animal models of chronic kidney disease suggesting that CRP actively increases inflammation (21,23). Despite all of this evidence of association, it is not known if CRP is causal in AKI.…”

mentioning

confidence: 99%

C-reactive protein exacerbates renal ischemia-reperfusion injury

Pegues

McCrory

Zarjou

et al. 2013

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

Pegues MA, McCrory MA, Zarjou A, Szalai AJ. C-reactive protein exacerbates renal ischemia-reperfusion injury. Am J Physiol Renal Physiol 304: F1358 -F1365, 2013. First published March 27, 2013 doi:10.1152/ajprenal.00476.2012.-Renal ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury (AKI), occurring with hypotension and cardiovascular surgery and inevitably during kidney transplantation. Mortality from AKI is high due to incomplete knowledge of the pathogenesis of IRI and the lack of an effective therapy. Inflammation accompanies IRI and increases the blood level of C-reactive protein (CRP), a biomarker of worsened outcomes in AKI. To test if CRP is causal in AKI we subjected wild-type mice (WT) and human CRP transgenic mice (CRPtg) to bilateral renal IRI (both pedicles clamped for 30 min at 37°C then reperfused for 24 h). Serum human CRP level was increased approximately sixfold after IRI in CRPtg (10.62 Ϯ 1.31 g/ml at baseline vs. 72.01 Ϯ 9.41 g/ml at 24 h) but was not elevated by sham surgery wherein kidneys were manipulated but not clamped. Compared with WT, serum creatinine, urine albumin, and histological evidence of kidney damage were increased after IRI in CRPtg mice. RT-PCR analysis of mRNA isolated from whole kidneys of CRPtg and WT subjected to IRI revealed that in CRPtg kidneys 1) upregulation of markers of macrophage classical activation (M1 markers) was blunted, 2) downregulation of markers of macrophage alternative activation (M2 markers) was more robust, and 3) expression of the activating receptor Fc␥RI was increased. Our finding that CRP exacerbates IRI-induced AKI, perhaps by shifting the balance of macrophage activation and Fc␥R expression towards a detrimental portfolio, might make CRP a promising therapeutic target for the treatment of AKI.alternatively activated macrophages; acute phase proteins; AKI ACUTE KIDNEY INJURY (AKI) can occur in any setting where renal ischemia reperfusion injury (IRI) is manifest, including during cardiovascular surgery (37) and kidney transplantation (50). In fact, AKI is a serious complication in ϳ1% of all hospitalizations and has a mortality rate as high as 80% (22,37). Despite this risk to patients and its burden on the health care system, there is still no effective therapy for AKI. The pathogenesis of renal IRI is not completely understood, but it is recognized that it is always accompanied by a systemic inflammatory response (35). Damage to the kidney is thought to evoke the release of inflammatory cytokines like TNF-␣ and IL-6 that in turn foster renal infiltration of leukocytes, neutrophils, dendritic cells, and macrophages (1,20). Exactly how this inflammatory cascade culminates in kidney damage and how this process is regulated are unknown.

show abstract

C-reactive protein promotes acute renal inflammation and fibrosis in unilateral ureteral obstructive nephropathy in mice

Cited by 65 publications

References 47 publications

Global miRNA expression and correlation with mRNA levels in primary human bone cells

Global miRNA expression and correlation with mRNA levels in primary human bone cells

The Long Pentraxin PTX3 Promotes Fibrocyte Differentiation

C-reactive protein exacerbates renal ischemia-reperfusion injury

Contact Info

Product

Resources

About