Alteration in the phenotype of macrophages in the repair of renal interstitial fibrosis in mice

Kushiyama, Taketoshi; Oda, Takashi; Yamada, Muneharu; Higashi, Keishi; Yamamoto, Kojiro; Sakurai, Yoshinori; Miura, Soichiro; Kumagai, Hiroo

doi:10.1111/j.1440-1797.2010.01439.x

Cited by 45 publications

(31 citation statements)

References 22 publications

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“…A large number of F4/80-positive cells were seen in the UUO kidneys ( Fig. 2A), which is in accordance with previous studies (Lai et al 2013;Kushiyama et al 2011). EGCG administration dramatically decreased the number of F4/80-positive cells.…”

Section: Egcg Ameliorates Inflammatory Responses In Uuo Micesupporting

confidence: 93%

Epigallocatechin-3-Gallate Attenuates Unilateral Ureteral Obstruction-Induced Renal Interstitial Fibrosis in Mice

Wang

et al. 2014

J Histochem Cytochem.

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The severity of tubulointerstitial fibrosis is regarded as an important determinant of renal prognosis. Therapeutic strategies targeting tubulointerstitial fibrosis have been considered to have potential in the treatment of chronic kidney disease. This study aims to evaluate the protective effects of (-)-epigallocatechin-3-gallate (EGCG), a green tea polyphenol, against renal interstitial fibrosis in mice. EGCG was administrated intraperitoneally for 14 days in a mouse model of unilateral ureteral obstruction (UUO). The results of our histological examination showed that EGCG alleviated glomerular and tubular injury and attenuated renal interstitial fibrosis in UUO mice. Furthermore, the inflammatory responses induced by UUO were inhibited, as represented by decreased macrophage infiltration and inflammatory cytokine production. Additionally, the expression of type I and III collagen in the kidney were reduced by EGCG, which indicated an inhibition of extracellular matrix accumulation. EGCG also caused an up-regulation in α-smooth muscle actin expression and a down-regulation in E-cadherin expression, indicating the inhibition of epithelial-to-mesenchymal transition. These changes were found to be in parallel with the decreased level of TGF-β1 and phosphorylated Smad. In conclusion, the present study demonstrates that EGCG could attenuate renal interstitial fibrosis in UUO mice, and this renoprotective effect might be associated with its effects of inflammatory responses alleviation and TGF-β/Smad signaling pathway inhibition.

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Section: Egcg Ameliorates Inflammatory Responses In Uuo Micesupporting

confidence: 93%

Epigallocatechin-3-Gallate Attenuates Unilateral Ureteral Obstruction-Induced Renal Interstitial Fibrosis in Mice

Wang

et al. 2014

J Histochem Cytochem.

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“…Renal interstitial fibrosis (RIF) is the final common pathway leading to chronic kidney diseases and end-stage renal disease [1,2], and its effective therapeutic strategy is wanting at present. Unilateral ureteral obstruction (UUO) is a well-characterized model of experimental obstructive nephropathy, culminating in RIF [3,4].…”

Section: Introductionmentioning

confidence: 99%

All-Trans Retinoic Acid Treatment Is Associated with Prohibitin Expression in Renal Interstitial Fibrosis Rats

Zhou

Qin

et al. 2012

IJMS

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This study was performed to investigate the association of prohibitin with renal interstitial fibrosis (RIF) lesion and to explore the association of all-trans retinoic acid (ATRA) treatment with prohibitin expression in RIF rats. Rats were divided into three groups: the sham operation group (SHO), the model group subjected to unilateral ureteral obstruction (UUO), and the model group treated with ATRA (GA). Renal tissues were collected at 14 and 28 days after surgery, and the relevant indicators were detected. In comparison with the SHO group, the RIF index in the UUO group was markedly elevated (p < 0.01), and the RIF index in the GA group was alleviated compared with that in the UUO group (p < 0.01). Compared with the SHO group, the expression of prohibitin (protein or mRNA) in the UUO group was significantly reduced (each p < 0.01). Prohibitin expression in the GA group was markedly increased when compared with that in the UUO (p < 0.01). The expression of TGF-β1 (protein and mRNA), protein expressions of Col-IV, fibronectin, α-SMA and cleaved Caspase-3, ROS generation and cell apoptosis index in the UUO group were markedly higher than those in the SHO group (all p < 0.01), and their expressions in the GA group were markedly down-regulated compared to those in the UUO group (all p < 0.01, respectively). The protein expression of prohibitin was negatively correlated with the RIF index, protein expression of TGF-β1, Col-IV, fibronectin, α-SMA or cleaved Caspase-3, ROS generation and the cell apoptosis index (each p < 0.01). In conclusion, lower expression of prohibitin is associated with the RIF, and ATRA treatment is associated with increased prohibitin, which can prevent the progression of RIF.

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“…16 MRC1 is a marker of alternatively activated M2 macrophages that is involved in collagen uptake, indicating its role in adaptive and maladaptive fibrosis. 22 All these results indicate that our candidates are not merely bystanders, with a random change in expression that just associates with the disease, but they are involved in pathophysiologic mechanisms that are important for the development of kidney fibrosis. It remains to be tested if some of the other candidates identified by our study play a mechanistic role in the development of kidney fibrosis and could offer future therapeutic targets, even as the lack of detection by SRM indicates that they probably do not have urinary biomarker potential.…”

Section: Discussionmentioning

confidence: 98%

RNA Sequencing Identifies Novel Translational Biomarkers of Kidney Fibrosis

Craciun

Bijol

Ajay

et al. 2015

JASN

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CKD is the gradual, asymptomatic loss of kidney function, but current tests only identify CKD when significant loss has already happened. Several potential biomarkers of CKD have been reported, but none have been approved for preclinical or clinical use. Using RNA sequencing in a mouse model of folic acidinduced nephropathy, we identified ten genes that track kidney fibrosis development, the common pathologic finding in patients with CKD. The gene expression of all ten candidates was confirmed to be significantly higher (approximately ten-to 150-fold) in three well established, mechanistically distinct mouse models of kidney fibrosis than in models of nonfibrotic AKI. Protein expression of these genes was also high in the folic acid model and in patients with biopsy-proven kidney fibrosis. mRNA expression of the ten genes increased with increasing severity of kidney fibrosis, decreased in response to therapeutic intervention, and increased only modestly (approximately two-to five-fold) with liver fibrosis in mice and humans, demonstrating specificity for kidney fibrosis. Using targeted selected reaction monitoring mass spectrometry, we detected three of the ten candidates in human urine: cadherin 11 (CDH11), macrophage mannose receptor C1 (MRC1), and phospholipid transfer protein (PLTP). Furthermore, urinary levels of each of these three proteins distinguished patients with CKD (n=53) from healthy individuals (n=53; P,0.05). In summary, we report the identification of urinary CDH11, MRC1, and PLTP as novel noninvasive biomarkers of CKD.

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Alteration in the phenotype of macrophages in the repair of renal interstitial fibrosis in mice

Abstract: Although the total number of infiltrating myofibroblasts and macrophages decreased after UUO release, the ratios of macrophages expressing CD204 and CD206 increased, suggesting that M2 macrophages play an important role in the repair of renal fibrosis.

Cited by 45 publications

References 22 publications

Epigallocatechin-3-Gallate Attenuates Unilateral Ureteral Obstruction-Induced Renal Interstitial Fibrosis in Mice

Epigallocatechin-3-Gallate Attenuates Unilateral Ureteral Obstruction-Induced Renal Interstitial Fibrosis in Mice

All-Trans Retinoic Acid Treatment Is Associated with Prohibitin Expression in Renal Interstitial Fibrosis Rats

RNA Sequencing Identifies Novel Translational Biomarkers of Kidney Fibrosis

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