MCP-1/CCR2 system is involved in high glucose-induced fibronectin and type IV collagen expression in cultured mesangial cells

Park, Jehyun; Ryu, Dong Ryeol; Li, Jin Ji; Jung, Dukyoo; Kwak, Seung Jae; Lee, Sun Ha; Yoo, Tae‐Hyun; Han, Seung Hyeok; Lee, Jung Eun; Kim, Yon Su; Moon, Sung Jin; Kim, Kunhong; Han, Dae Suk; Kang, Shin Wook

doi:10.1152/ajprenal.00547.2007

Cited by 51 publications

(50 citation statements)

References 38 publications

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“…Collagen metabolism disorders play an important role in the pathogenesis of DN. 19 TGF-b1 is considered an important etiologic factor in interstitial fibrosis by increasing the production of ECM. In addition, its upregulation is a common characteristic of renal tubulointerstitial fibrosis in DN.…”

Section: Effects Of Nctd On Can/nfatc Signaling Pathway In Hk-2 Cellsmentioning

confidence: 99%

Norcantharidin inhibits the expression of extracellular matrix and TGF-β1 in HK-2 cells induced by high glucose independent of calcineurin signal pathway

Chen

Liu

et al. 2011

Laboratory Investigation

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Norcantharidin (NCTD) was shown in our previous studies to attenuate renal tubulointerstitial fibrosis in rat models with diabetic nephropathy (DN). The aim of this study was to determine the effects of NCTD on the expression of extracellular matrix (ECM) and TGF-b1 in HK-2 cells stimulated by high glucose and on calcineurin (CaN)/NFAT pathway. Whether or not the antifibrotic effect of NCTD on renal interstitium was dependent on its inhibition of CaN pathway was also investigated. Experimental concentrations of NCTD were verified by cytotoxic test and MTT assay. HK-2 cells were transfected with CaN small interference RNA (siRNA). The mRNA and protein expressions of FN, ColIV, TGF-b1, and CaN in HK-2 cells were detected by real-time PCR and western blot. The CaN/NFAT pathway was examined by indirect immunofluorescence and western blot. Our study revealed that NCTD concentrations over 5 mg/l had overt cytotoxicity on HK-2 cells. Meanwhile, both 2.5 and 5 mg/l NCTD inhibited HK-2 cell proliferation (Po0.05). NCTD inhibited the upregulation of FN, ColIV, and TGF-b1 of HK-2 cells stimulated by high glucose (Po0.05), and also significantly downregulated the expression of CaN mRNA and protein in HK-2 cells (Po0.05). In addition, not only was the nuclear translocation of NFATc inhibited, but its protein level in the nucleus was also reduced. Following CaN siRNA transfection, CaN mRNA and protein expression were significantly decreased. In contrast, the protein levels of FN, ColIV, and TGF-b1 increased in HK-2 cells stimulated by high glucose (Po0.05). However, NCTD treatment downregulated their expression. These results indicated that NCTD could decrease the expression of ECM and TGF-b1 in HK-2 cells stimulated by high glucose, downregulate CaN expression, and block the CaN/NFAT signaling pathway. However, the effect of NCTD on inhibition of the expression of ECM and TGF-b1 was not associated with its inhibition of the CaN/NFAT pathway.

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Section: Effects Of Nctd On Can/nfatc Signaling Pathway In Hk-2 Cellsmentioning

confidence: 99%

Norcantharidin inhibits the expression of extracellular matrix and TGF-β1 in HK-2 cells induced by high glucose independent of calcineurin signal pathway

Chen

Liu

et al. 2011

Laboratory Investigation

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“…MCP-1 directly increased fibronectin production in cultured mesangial cells. 17,19 Recently, we also found that MCP-1 directly induced podocyte apoptosis. 18 In addition, MCP-1 itself induced intercellular adhesion molecule-1 and fibronectin expression in cultured mesangial cells.…”

Section: Discussionmentioning

confidence: 93%

“…17 The kits for human MCP-1 were species specific and sensitive up to 5.0 pg/ml. The minimum sensitivity for human TGF-b1 of the kit used in this study was 4.6 pg/ml.…”

Section: Elisamentioning

confidence: 99%

“…21 In addition, a close interaction between TGF-b1 and MCP-1 has also been identified in vitro in cultured mesangial cells and podocytes. 17,22 Based on these findings, we hypothesized that the impact of the MCP-1/ CCR2 system on EMT of PMCs and ECM accumulation synthesis was associated with the TGF-b1 pathway. In the present study, MCP-1 directly increased TGF-b1 production in cultured HPMCs and MCP-1-induced EMT and fibronectin expression were ameliorated by anti-TGF-b1 antibody.…”

Section: Mcp1 and Peritoneal Fibrosismentioning

confidence: 99%

“…[14][15][16] In addition, several recent studies have shown that there may be an intrinsic regulatory loop between MCP-1 and TGF-b1. [17][18][19][20][21][22] To our knowledge, however, no study has investigated if there is a direct association between the MCP-1/ CCR2 system and TGF-b1 in PMCs. Moreover, the direct effect of MCP-1 on EMT and ECM synthesis has never been elucidated in these cells.…”

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confidence: 99%

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The monocyte chemoattractant protein-1 (MCP-1)/CCR2 system is involved in peritoneal dialysis-related epithelial–mesenchymal transition of peritoneal mesothelial cells

Lee

Kang

Kim

et al. 2012

Laboratory Investigation

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Epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells (PMCs) has a role in the process of peritoneal fibrosis (PF), a serious complication in peritoneal dialysis (PD) patients. Even though monocyte chemoattractant protein-1 (MCP-1) was demonstrated to directly increase extracellular matrix (ECM) synthesis, the role of the MCP-1/CCR2 system in PD-related EMT and ECM synthesis in cultured human PMCs (HPMCs) and in an animal model of PD has never been elucidated. In vitro, HPMCs were exposed to 5.6 mM glucose (NG), NG þ MCP-1 (10 ng/ml) (NG þ MCP-1), or 100 mM glucose (HG) with or without CCR2 inhibitor (RS102895) (CCR2i) or a dominant-negative mutant MCP-1-expressing lentivirus (LV-mMCP-1). In vivo, PD catheters were inserted into 60 Sprague-Dawley rats, and saline (Control, C) (N ¼ 30) or 4.25% PD solution (PD) (N ¼ 30) was infused for 4 weeks. Twenty rats from each group were treated with empty LV or LVmMCP-1 intraperitoneally. Snail, E-cadherin, a-smooth muscle actin (a-SMA), and fibronectin protein expression in HPMCs and the peritoneum was evaluated by western blot analysis. Compared with NG cells, Snail, a-SMA, and fibronectin expression was significantly increased, while E-cadherin expression was significantly decreased in HPMCs exposed to HG and NG þ MCP-1, and these changes were significantly abrogated by CCR2i (Po0.05). In addition, MCP-1-induced EMT was significantly attenuated by anti-TGF-b1 antibody. In PD rats, Snail and fibronectin expression was significantly increased in the peritoneum, whereas the ratios of E-cadherin/a-SMA protein expression were significantly decreased (Po0.05). The thickness of the peritoneum and the intensity of Masson's trichrome staining in the peritoneum were also significantly higher in PD rats than in C rats (Po0.05). These changes in PD rats were significantly abrogated by LV-mMCP-1. These findings suggest that the MCP-1/CCR2 system is directly involved in PD-related EMT and ECM synthesis and that this is mediated, at least in part, via TGF-b1.

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Monocyte chemoattractant protein-1 and the blood–brain barrier

Yao

Tsirka

2013

Cell. Mol. Life Sci.

155

121

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Blood-Brain Barrier (BBB) is a dynamic structure that maintains the homeostasis of the brain and thus proper neurological functions. BBB compromise has been found in many pathological conditions, including neuroinflammation. Monocyte chemoattractant protein-1 (MCP1), a chemokine that is transiently and significantly up-regulated during inflammation, is able to disrupt the integrity of BBB and modulate the progression of various diseases, including excitotoxic injury and hemorrhage. In this review, we first introduce the biochemistry and biology of MCP1, and then summarize the effects of MCP1 on BBB integrity as well as individual BBB components.

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MCP-1/CCR2 system is involved in high glucose-induced fibronectin and type IV collagen expression in cultured mesangial cells

Cited by 51 publications

References 38 publications

Norcantharidin inhibits the expression of extracellular matrix and TGF-β1 in HK-2 cells induced by high glucose independent of calcineurin signal pathway

Norcantharidin inhibits the expression of extracellular matrix and TGF-β1 in HK-2 cells induced by high glucose independent of calcineurin signal pathway

The monocyte chemoattractant protein-1 (MCP-1)/CCR2 system is involved in peritoneal dialysis-related epithelial–mesenchymal transition of peritoneal mesothelial cells

Monocyte chemoattractant protein-1 and the blood–brain barrier

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