Identification of an alternative splicing transcript for the resistin gene and distribution of its mRNA in human tissue

Nohira, Tomoyoshi; Nagao, Kumi; Kameyama, Kazuhisa; Nakai, Hiromi; Fukumine, Noritaka; Okabe, Kazuhiro; Kitano, Soichi; Higuchi, Hisashi

doi:10.1530/eje.0.1510151

Cited by 38 publications

(25 citation statements)

References 24 publications

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“…An alternative explanation is that IGF-I may modulate the respective splicing and processing events of Rstn mRNA and protein and thereby lead to translocation of the Rstn protein, accumulation of the nonsecretable Rstn isoform, and a decrease in Rstn protein release. This assumption can be indirectly supported by recent evidence that a novel nonsecretable Rstn isoform lacking the exon 2 component has been reported in adipose tissues of Wistar rats (2), mice, and humans (34).…”

Section: Discussionmentioning

confidence: 71%

IGF-I downregulates resistin gene expression and protein secretion

Chen

Hung

Kao

2005

American Journal of Physiology-Endocrinology and Metabolism

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Section: Discussionmentioning

confidence: 71%

IGF-I downregulates resistin gene expression and protein secretion

Chen

Hung

Kao

2005

American Journal of Physiology-Endocrinology and Metabolism

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“…RELM␤ expression is induced in the human colon cancer cell line LS174T by treatment with recombinant human IL-4 or IL-13 (1, 10), suggesting a potential role in the Th2 immune response. It is interesting to note that an alternative splice variant to a related molecule, resistin, is expressed in human lung (24). One previous study demonstrated that resistin can induce both mitogenesis and migration of human lung microvascular endothelial cells in vitro (23), and another showed that resistin induces proliferation of cultured human vascular smooth muscle cells (3).…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELMα) induces the vascular and hemodynamic changes of pulmonary hypertension

Angelini¹,

Su²,

Yamaji-Kegan³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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Pulmonary hypertension (PH) is a serious disease of multiple etiologies mediated by hypoxia, immune stimuli, and elevated pulmonary pressure that leads to vascular thickening and eventual right heart failure. In a chronic hypoxia model of PH, we previously reported the induction of a novel pleiotropic cytokine, hypoxia-induced mitogenic factor (HIMF), that exhibits mitogenic, vasculogenic, contractile, and chemokine properties during PH-associated vascular remodeling. To examine the role of HIMF in hypoxia-induced vascular remodeling, we performed in vivo knockdown of HIMF using short hairpin RNA directed at rat HIMF in the chronic hypoxia model of PH. Knockdown of HIMF partially blocked increases in mean pulmonary artery pressure, pulmonary vascular resistance, right heart hypertrophy, and vascular remodeling caused by chronic hypoxia. To demonstrate a direct role for HIMF in the mechanism of PH development, we performed HIMF-gene transfer into the lungs of rats using a HIMF-expressing adeno-associated virus (AAV). AAV-HIMF alone caused development of PH similar to that of chronic hypoxia with increased mean pulmonary artery pressure and pulmonary vascular resistance, right heart hypertrophy, and neomuscularization and thickening of small pulmonary arterioles. The findings suggest that HIMF represents a critical cytokine-like growth factor in the development of PH.

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“…This suggests the importance of the dimerization of Rstn in the regulation of adipogenesis. Recent evidence showed that secretable and nonsecretable Rstn isoforms were reported in adipose tissues of rats, mice, and humans (3,34). Thus it would be worthwhile in a future study to explore whether EGCG modulates the respective splicing and processing events of Rstn mRNA and protein and thereby leads to translocation of the Rstn protein.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effect of green tea (−)-epigallocatechin gallate on resistin gene expression in 3T3-L1 adipocytes depends on the ERK pathway

Liu

Chen

Hung

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

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is known as an adipocyte-specific secretory hormone that can cause insulin resistance and decrease adipocyte differentiation. By contrast, green tea catechins, especially (Ϫ)-epigallocatechin gallate (EGCG), have been reported as body weight and diabetes chemopreventatives. Whether EGCG regulates production of Rstn is unknown. Using 3T3-L1 adipocytes, we found that EGCG at 20 and 100 M suppressed Rstn mRNA levels by ϳ35 and 50%, respectively, after 3 h. The basal half-life of Rstn mRNA induced by actinomycin D was Ͼ12 h but shifted to 3 h in the presence of EGCG. This suggests that EGCG regulates the stability of Rstn mRNA. Treatment with cycloheximide did not prevent EGCGsuppressed Rstn mRNA levels, which suggests that the effect of EGCG does not require new protein synthesis. Intracellular Rstn protein significantly decreased in the presence of 100 M EGCG 3 h after treatment, whereas the release of the Rstn protein did not significantly change. This suggests that EGCG may modulate the distribution of Rstn protein between the intracellular and extracellular compartments. EGCG did not affect the amounts of extracellular signal-related kinase-1/2 (ERK1/2), phospho-JNK, phospho-p38, and phospho-Akt proteins but reduced the amounts of phospho-ERK1/2 proteins. Overexpression with MEK1 blocked EGCG-inhibited Rstn mRNA expression. These data suggest that EGCG downregulates Rstn expression via a pathway that is dependent on the ERK pathway.genistein; mitogen-activated protein kinase; extracellular signal-related kinase RESISTIN (RSTN) IS A CYSTEINE-RICH POLYPEPTIDE HORMONE (20,38) that, depending on the species, contains 4 -5 exons, 3-4 introns, 575-1217 bp of mRNA, and 108 -114 amino acids of protein (10 -12.5 kDa) (16,23,44,45). Rstn is first isolated from adipose tissues and found to link obesity to type 2 diabetes (44). In particular, Rstn mRNA expression in adipose tissues of obese humans is higher than that in normal subjects (12). In addition, a single nucleotide polymorphism in the Rstn gene promoter is associated with obesity (14) and diabetes (35), and the plasma Rstn levels are elevated in patients with obesity (12) and type 2 diabetes (59). Moreover, the dominant negative form of Rstn enhances adipogenesis and improves insulin sensitivity (24). Ever since its discovery, Rstn also has been found to possess numerous other actions. For example, Rstn regulates fasted blood glucose (6), causes dyslipidemia (39), suppresses insulin-stimulated glucose uptake in adipocytes (44) and muscle cells (30), inhibits dopamine and norepinephrine release in the hypothalamus (8), and promotes endothelial cell activation (50) and smooth muscle proliferation (9). To our knowledge, the expression of Rstn gene can be regulated by nutritional, endocrine, genetic, pharmacological, and developmental factors (5), and the mechanisms of action of Rstn are emerging. For example, Rstn promotes smooth muscle cell proliferation through the activation of extracellular signalregulated kinase (ERK1/2) and phosphatidylinositol 3-kinase (PI3K) ...

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Identification of an alternative splicing transcript for the resistin gene and distribution of its mRNA in human tissue

Cited by 38 publications

References 24 publications

IGF-I downregulates resistin gene expression and protein secretion

IGF-I downregulates resistin gene expression and protein secretion

Hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELMα) induces the vascular and hemodynamic changes of pulmonary hypertension

Inhibitory effect of green tea (−)-epigallocatechin gallate on resistin gene expression in 3T3-L1 adipocytes depends on the ERK pathway

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