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Opposite Expression of SPARC between the Liver and Pancreas in Streptozotocin-Induced Diabetic Rats.

Aseer KR, Kim SW, Choi MS, Yun JW - PLoS ONE (2015)

Bottom Line: Diabetic liver showed significant up-regulation of Tgfb1 as well as moderately less up-regulated TNFα and reduced Fn1, resulting in elevated fibrogenesis.PARP-1 was not up-regulated during CD95-mediated apoptosis, resulting in restoration of high ATP levels in the diabetic liver.High and low cellular insulin content was found in the diabetic liver and pancreas, respectively.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology, Daegu University, Kyungsan, Kyungbuk, 712-714, Republic of Korea.

ABSTRACT
Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that regulates several cellular events, including inflammation and tissue remodelling. In this study, we investigated the tissue-specific expression of SPARC in streptozotocin (STZ)-induced diabetes, and found that SPARC was significantly up-regulated in the liver while down-regulated in the pancreas of STZ-induced diabetic rats. Chronic inflammation occurred in the diabetic pancreas accompanied by up-regulation of CCAAT/enhancer-binding protein beta (C/EBPβ) and its targets (TNFα, Il6, CRP, and Fn1) as well as myeloperoxidase (Mpo) and C-X-C chemokine receptor type 2 (Cxcr2). Diabetic liver showed significant up-regulation of Tgfb1 as well as moderately less up-regulated TNFα and reduced Fn1, resulting in elevated fibrogenesis. PARP-1 was not up-regulated during CD95-mediated apoptosis, resulting in restoration of high ATP levels in the diabetic liver. On the contrary, CD95-dependent apoptosis was not observed in the diabetic pancreas due to up-regulation of PARP-1 and ATP depletion, resulting in necrosis. The cytoprotective machinery was damaged by pancreatic inflammation, whereas adequate antioxidant capacity indicates low oxidative stress in the diabetic liver. High and low cellular insulin content was found in the diabetic liver and pancreas, respectively. Furthermore, we identified six novel interacting partner proteins of SPARC by co-immunoprecipitation in the diabetic liver and pancreas, and their interactions with SPARC were predicted by bioinformatics tools. Taken together, opposite expression of SPARC in the diabetic liver and pancreas may be related to inflammation and immune cell infiltration, degrees of apoptosis and fibrosis, cytoprotective machinery, and cellular insulin levels.

No MeSH data available.


Related in: MedlinePlus

Tissue-dependent protein expression levels of MCP-1, iNOS, NFκB, Cyt C, PARP-1 ATP5B, and CD95 in liver (A and C) and pancreas (B and D), respectively.Data are representative of three independent experiments. Statistical significance between male and female rats was calculated by One-way ANOVA followed by Tukey’s post hoc tests, where p-value is *p<0.05 and **p<0.01, and significance between controls and diabetics is represented by †p<0.05 and ††p<0.01.
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pone.0131189.g004: Tissue-dependent protein expression levels of MCP-1, iNOS, NFκB, Cyt C, PARP-1 ATP5B, and CD95 in liver (A and C) and pancreas (B and D), respectively.Data are representative of three independent experiments. Statistical significance between male and female rats was calculated by One-way ANOVA followed by Tukey’s post hoc tests, where p-value is *p<0.05 and **p<0.01, and significance between controls and diabetics is represented by †p<0.05 and ††p<0.01.

Mentions: We observed tissue-specific regulation of Tgfb1 expression in the diabetic liver and pancreas. The mRNA expression of Tgfb1 was strikingly up-regulated in the diabetic liver (Fig 3C), whereas it was significantly down-regulated in the diabetic pancreas (Fig 3D). The mRNA expression of immune cell infiltration markers myeloperoxidase (Mpo) and C-X-C chemokine receptor type 2 (Cxcr2) markedly increased in the diabetic livers of male rats. On the contrary, these levels were significantly attenuated in the livers of STZ-induced female rats and showed clear gender dimorphism (Fig 3C). The mRNA expression of Mpo and Cxcr2 was highly up-regulated in the diabetic pancreas of both genders (Fig 3D). Thus, these findings may be relevant in the context of Tgfb1 activity in infiltrating immune cells, which may be associated with opposite regulation of SPARC in the diabetic liver and pancreas. Regardless of the tissue-specific expression patterns of other inflammatory mediators, interleukin-1 beta (Il1b) gene, monocyte chemoattractant protein 1 (MCP-1), nitric oxide synthase (iNOS), nuclear factor kappa B (NFκB), and cytochrome C oxidase (Cyt C) were up-regulated in the diabetic liver and pancreas (Fig 3C and 3D and Fig 4A and 4B) of both genders. Remarkably, all of these proteins/genes showed relatively less up-regulation only in the diabetic liver of females as compared to diabetic male rats.


Opposite Expression of SPARC between the Liver and Pancreas in Streptozotocin-Induced Diabetic Rats.

Aseer KR, Kim SW, Choi MS, Yun JW - PLoS ONE (2015)

Tissue-dependent protein expression levels of MCP-1, iNOS, NFκB, Cyt C, PARP-1 ATP5B, and CD95 in liver (A and C) and pancreas (B and D), respectively.Data are representative of three independent experiments. Statistical significance between male and female rats was calculated by One-way ANOVA followed by Tukey’s post hoc tests, where p-value is *p<0.05 and **p<0.01, and significance between controls and diabetics is represented by †p<0.05 and ††p<0.01.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4481468&req=5

pone.0131189.g004: Tissue-dependent protein expression levels of MCP-1, iNOS, NFκB, Cyt C, PARP-1 ATP5B, and CD95 in liver (A and C) and pancreas (B and D), respectively.Data are representative of three independent experiments. Statistical significance between male and female rats was calculated by One-way ANOVA followed by Tukey’s post hoc tests, where p-value is *p<0.05 and **p<0.01, and significance between controls and diabetics is represented by †p<0.05 and ††p<0.01.
Mentions: We observed tissue-specific regulation of Tgfb1 expression in the diabetic liver and pancreas. The mRNA expression of Tgfb1 was strikingly up-regulated in the diabetic liver (Fig 3C), whereas it was significantly down-regulated in the diabetic pancreas (Fig 3D). The mRNA expression of immune cell infiltration markers myeloperoxidase (Mpo) and C-X-C chemokine receptor type 2 (Cxcr2) markedly increased in the diabetic livers of male rats. On the contrary, these levels were significantly attenuated in the livers of STZ-induced female rats and showed clear gender dimorphism (Fig 3C). The mRNA expression of Mpo and Cxcr2 was highly up-regulated in the diabetic pancreas of both genders (Fig 3D). Thus, these findings may be relevant in the context of Tgfb1 activity in infiltrating immune cells, which may be associated with opposite regulation of SPARC in the diabetic liver and pancreas. Regardless of the tissue-specific expression patterns of other inflammatory mediators, interleukin-1 beta (Il1b) gene, monocyte chemoattractant protein 1 (MCP-1), nitric oxide synthase (iNOS), nuclear factor kappa B (NFκB), and cytochrome C oxidase (Cyt C) were up-regulated in the diabetic liver and pancreas (Fig 3C and 3D and Fig 4A and 4B) of both genders. Remarkably, all of these proteins/genes showed relatively less up-regulation only in the diabetic liver of females as compared to diabetic male rats.

Bottom Line: Diabetic liver showed significant up-regulation of Tgfb1 as well as moderately less up-regulated TNFα and reduced Fn1, resulting in elevated fibrogenesis.PARP-1 was not up-regulated during CD95-mediated apoptosis, resulting in restoration of high ATP levels in the diabetic liver.High and low cellular insulin content was found in the diabetic liver and pancreas, respectively.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology, Daegu University, Kyungsan, Kyungbuk, 712-714, Republic of Korea.

ABSTRACT
Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that regulates several cellular events, including inflammation and tissue remodelling. In this study, we investigated the tissue-specific expression of SPARC in streptozotocin (STZ)-induced diabetes, and found that SPARC was significantly up-regulated in the liver while down-regulated in the pancreas of STZ-induced diabetic rats. Chronic inflammation occurred in the diabetic pancreas accompanied by up-regulation of CCAAT/enhancer-binding protein beta (C/EBPβ) and its targets (TNFα, Il6, CRP, and Fn1) as well as myeloperoxidase (Mpo) and C-X-C chemokine receptor type 2 (Cxcr2). Diabetic liver showed significant up-regulation of Tgfb1 as well as moderately less up-regulated TNFα and reduced Fn1, resulting in elevated fibrogenesis. PARP-1 was not up-regulated during CD95-mediated apoptosis, resulting in restoration of high ATP levels in the diabetic liver. On the contrary, CD95-dependent apoptosis was not observed in the diabetic pancreas due to up-regulation of PARP-1 and ATP depletion, resulting in necrosis. The cytoprotective machinery was damaged by pancreatic inflammation, whereas adequate antioxidant capacity indicates low oxidative stress in the diabetic liver. High and low cellular insulin content was found in the diabetic liver and pancreas, respectively. Furthermore, we identified six novel interacting partner proteins of SPARC by co-immunoprecipitation in the diabetic liver and pancreas, and their interactions with SPARC were predicted by bioinformatics tools. Taken together, opposite expression of SPARC in the diabetic liver and pancreas may be related to inflammation and immune cell infiltration, degrees of apoptosis and fibrosis, cytoprotective machinery, and cellular insulin levels.

No MeSH data available.


Related in: MedlinePlus