Role of cyclooxygenase-2 in the development of interstitial fibrosis in kidneys following unilateral ureteral obstruction in mice

Hosono, Kanako; Fujita, Tomoe; Kamata, Kouju; Murakami, Masataka

doi:10.1016/j.biopha.2015.01.010

Cited by 20 publications

(22 citation statements)

References 26 publications

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“…Recently, Nilsson et al (44) reported that global COX-2 deficiency exacerbated unilateral ureteral obstruction (UUO)–induced kidney damage. Similarly, Kamata et al (45) reported that inhibition of COX-2 activity with celecoxib exacerbated development of fibrosis in UUO kidneys. However, COX-2 knockdown in macrophages using a chitosan delivery system was reported to attenuate UUO-induced kidney damage in association with decreases in inflammation, oxidative stress, and apoptosis (46).…”

Section: Discussionmentioning

confidence: 89%

Macrophage Cyclooxygenase-2 Protects Against Development of Diabetic Nephropathy

et al. 2016

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Diabetic nephropathy (DN) is characterized by increased macrophage infiltration, and proinflammatory M1 macrophages contribute to development of DN. Previous studies by us and others have reported that macrophage cyclooxygenase-2 (COX-2) plays a role in polarization and maintenance of a macrophage tissue-reparative M2 phenotype. We examined the effects of macrophage COX-2 on development of DN in type 1 diabetes. Cultured macrophages with COX-2 deletion exhibited an M1 phenotype, as demonstrated by higher inducible nitric oxide synthase and nuclear factor-κB levels but lower interleukin-4 receptor-α levels. Compared with corresponding wild-type diabetic mice, mice with COX-2 deletion in hematopoietic cells (COX-2 knockout bone marrow transplantation) or macrophages (CD11b-Cre COX2f/f) developed severe DN, as indicated by increased albuminuria, fibrosis, and renal infiltration of T cells, neutrophils, and macrophages. Although diabetic kidneys with macrophage COX-2 deletion had more macrophage infiltration, they had fewer renal M2 macrophages. Diabetic kidneys with macrophage COX-2 deletion also had increased endoplasmic reticulum stress and decreased number of podocytes. Similar results were found in diabetic mice with macrophage PGE2 receptor subtype 4 deletion. In summary, these studies have demonstrated an important but unexpected role for macrophage COX-2/prostaglandin E2/PGE2 receptor subtype 4 signaling to lessen progression of diabetic kidney disease, unlike the pathogenic effects of increased COX-2 expression in intrinsic renal cells.

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Section: Discussionmentioning

confidence: 89%

Macrophage Cyclooxygenase-2 Protects Against Development of Diabetic Nephropathy

et al. 2016

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“…In line with this, OSU-03012, a non-cyclooxygenase-inhibiting celecoxib derivative, promotes apoptosis and inhibits activation of LX-2 cells [60]. The deleterious effects of COX-2 inhibition on fibrosis progression were also reported in kidney [61] and lung [62]. The antifibrotic role of PGE 2 on pulmonary fibrosis is achieved by inhibiting fibroblast proliferation, synthesis of collagen and modulation of TGF--induced transition of fibroblasts to myofibroblasts [63].…”

Section: Mcp-1) After MCD Mcp-1 Is a Potent Chemoattractant Mediatormentioning

confidence: 83%

Cyclooxygenase-2 expression in hepatocytes attenuates non-alcoholic steatohepatitis and liver fibrosis in mice

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et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Cyclooxygenase-2 (COX-2) is involved in different liver diseases but little is known about the significance of COX-2 in the development and progression of non-alcoholic steatohepatitis (NASH). This study was designed to elucidate the role of COX-2 expression in hepatocytes in the pathogenesis of steatohepatitis and hepatic fibrosis. In the present work, hepatocyte-specific COX-2 transgenic mice (hCOX-2-Tg) and their wild-type (Wt) littermates were either fed methionine-and-choline deficient (MCD) diet to establish an experimental non-alcoholic steatohepatitis (NASH) model or injected with carbon tetrachloride (CCl4) to induce liver fibrosis. In our animal model, hCOX-2-Tg mice fed MCD diet showed lower grades of steatosis, ballooning and inflammation than Wt mice, in part by reduced recruitment and infiltration of hepatic macrophages, with a corresponding decrease in serum levels of pro-inflammatory cytokines. Furthermore, hCOX-2-Tg mice showed a significant attenuation of the MCD diet-induced increase in oxidative stress and hepatic apoptosis observed in Wt mice. Even more, hCOX-2-Tg mice treated with CCl4 had significantly lower stages of fibrosis and less hepatic content of collagen, hydroxyproline and pro-fibrogenic markers than Wt controls. Collectively, our data indicates that constitutive hepatocyte COX-2 expression ameliorates NASH and liver fibrosis development in mice by reducing inflammation, oxidative stress and apoptosis and by modulating activation of hepatic stellate cells, respectively, suggesting a possible protective role for COX-2 induction in NASH/NAFLD progression.

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“…[3][4][5]17 It has been reported that the collagen level in the kidneys of UUO model mice is increased significantly, compared to that of the sham operated mice. 5 Using this method, the Hyp concentrations in the kidneys of six UUO model and sham mice were determined. As shown in Fig.…”

Section: Application Of Determination Of Hyp Of Uuo Model Micementioning

confidence: 99%

“…Since the Hyp content can be determined to evaluate the collagen levels that provide an indication of fibrosis, thus estimating the level of Hyp in tissue should be important for understanding the status of fibrosis. [3][4][5] To measure the concentrations of Hyp in biological samples or food, various methods have been developed, such as highperformance liquid chromatography (HPLC) with derivatization for fluorescence detection and high-performance liquid chromatography with tandem mass spectrometric detection (LC/ MS/MS). [6][7][8][9][10][11][12][13] We have developed an analytical method for the determination of urinary Hyp in rat.…”

Section: Introductionmentioning

confidence: 99%

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Bioanalytical Method for the Determination of Hydroxyproline in Mouse Kidney by High-Performance Liquid Chromatography with Tandem Mass Spectrometric Detection

et al. 2017

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An analytical method was developed and validated for the measurement of hydroxyproline (Hyp) levels in mouse kidney by high-performance liquid chromatography with tandem mass spectrometric detection (LC/MS/MS) using an analytical column specially designed for the LC/MS/MS analysis for intact amino acids. Tissue hydrolyzed with hydrochloric acid could be directly injected into the LC/MS/MS, as well as separated and detected using the deuterium labelled Hyp as an internal standard. The calibration curve showed good linearity from 5 to 500 nmol/mg of tissue; the precision and accuracy, including within-and between-run, were less than 6% and within 100 ± 6%, respectively.

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Role of cyclooxygenase-2 in the development of interstitial fibrosis in kidneys following unilateral ureteral obstruction in mice

Cited by 20 publications

References 26 publications

Macrophage Cyclooxygenase-2 Protects Against Development of Diabetic Nephropathy

Macrophage Cyclooxygenase-2 Protects Against Development of Diabetic Nephropathy

Cyclooxygenase-2 expression in hepatocytes attenuates non-alcoholic steatohepatitis and liver fibrosis in mice

Bioanalytical Method for the Determination of Hydroxyproline in Mouse Kidney by High-Performance Liquid Chromatography with Tandem Mass Spectrometric Detection

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