Pentraxin-3 Attenuates Renal Damage in Diabetic Nephropathy by Promoting M2 Macrophage Differentiation

Sun, Huaibin; Tian, Jun; Xian, Wanhua; Xie, Tingting; Yang, Xiaoling

doi:10.1007/s10753-015-0151-z

Cited by 45 publications

(35 citation statements)

References 34 publications

(34 reference statements)

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“…Similarly, pentraxin-3 polarized macrophages to an M2 phenotype and ameliorated experimental diabetic renal injury (39). In addition, suppression of renal M1 macrophages by deletion of Toll-like receptors 2 or 4 also protected against development of DN in mice (40,41).…”

Section: Discussionmentioning

confidence: 99%

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: 99%

Macrophage Cyclooxygenase-2 Protects Against Development of Diabetic Nephropathy

et al. 2016

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“…But at the same time it has been shown that diabetic vascular complications apart from DR also affect the serum levels of PTX3 protein. [38][39][40] Another limitation of our study was its relatively small sample size. It was because of PTX3 levels might be affected by several systemic diseases such as cardiovascular or cerebrovascular diseases, chronic kidney and liver failure, autoimmune disorders, irregular systemic hypertension.…”

Section: Eyementioning

confidence: 98%

Aqueous humor pentraxin-3 levels in patients with diabetes mellitus

Mutlu

Yüksel

Takmaz

et al. 2017

Eye

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PurposeTo evaluate aqueous humor (AH) pentraxin-3 (PTX3) levels in diabetic patients with and without diabetic retinopathy (DR).MethodsIn this prospective study, patients undergoing cataract surgery were enrolled. The study group was composed of 26 type-2 diabetic patients without DR (group 1), 32 diabetic patients with DR (group 2) and 29 age-matched subjects without any systemic disease (group 3). Fifteen proliferative DR (PDR) and 17 non-proliferative DR (NPDR) patients were enrolled in Group 2. HbA1c levels and duration of diabetes were noted. AH samples were obtained from anterior chamber at the beginning of cataract surgery and PTX3 levels were analyzed with Elisa kit.ResultsBaseline demographic characteristics were similar between groups. The mean duration of diabetes was 11.9±7.9 years in group 1 and 15.8±7.8 years in group 2 (P=0.11). The mean plasma HbA1c levels in group 1 was 9.1±2.6 and 8.2±2.4 in group 2 (P=0.36). PTX3 levels were 5.75±0.41 in group 1, 6.11±1.47 in group 2 and 4.93±0.84 ng/ml in group 3 (P=0.01). PTX3 levels in group 2 were higher than in group 1 and 3 (P=0.06 and P=0.01, respectively). There was no correlation between HbA1c and PTX3 levels (P=0.06 r=0.57, P=0.19 r=0.3, respectively). The mean PTX3 was 6.6±0.3 in PDR group and 5.6±0.5 ng/ml in NPDR group (P=0.04).ConclusionsPTX3 is an important marker especially for vascular endothelial damage. Since diabetic vascular changes are dependent on endothelial cell damage, high levels of AH PTX3 of DR patients may indicate the importance of PTX3 protein in the pathogenesis of DR.

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“…Recent studies have shown the protective role of PTX3 in nephropathy. PTX3 attenuated renal damage in mice with DN by promoting M2 macrophage differentiation 10. Therefore, it is hypothesized that PTX3 may be involved in the pathogenesis of DN development.…”

Section: Introductionmentioning

confidence: 99%

Association of Serum Pentraxin 3 Concentrations with Diabetic Nephropathy

Wang

Jietao

2016

Journal of Investigative Medicine

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Pentraxin 3 (PTX3), a member of a superfamily of conserved proteins, attenuates renal damage in diabetic mice. This study aims to determine whether serum PTX3 concentrations are correlated with the presence of diabetic nephropathy (DN). A total of 160 patients with type 2 diabetes mellitus (T2DM) and 54 healthy subjects were enrolled in this study. Patients with T2DM were divided into three groups in accordance with the levels of urinary albumin excretion (UAE). Serum PTX3 concentrations were determined using an ELISA kit. Serum PTX3 concentrations were significantly higher in patients with T2DM compared with the controls. Patients with T2DM with macroalbuminuria showed higher serum PTX3 concentrations compared with the other three groups. However, there were no significant differences of serum PTX3 concentrations between patients with T2DM with normoalbuminuria and microalbuminuria. Furthermore, a simple regression analysis has shown that serum PTX3 concentrations in patients with T2DM were negatively correlated with body mass index, and positively correlated with blood urea nitrogen, serum creatinine, and UAE. Serum PTX3 concentrations are correlated with DN.

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Pentraxin-3 Attenuates Renal Damage in Diabetic Nephropathy by Promoting M2 Macrophage Differentiation

Cited by 45 publications

References 34 publications

Macrophage Cyclooxygenase-2 Protects Against Development of Diabetic Nephropathy

Macrophage Cyclooxygenase-2 Protects Against Development of Diabetic Nephropathy

Aqueous humor pentraxin-3 levels in patients with diabetes mellitus

Association of Serum Pentraxin 3 Concentrations with Diabetic Nephropathy

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