Globular Adiponectin Activates Nuclear Factor-κB and Activating Protein-1 and Enhances Angiotensin II–Induced Proliferation in Cardiac Fibroblasts

Hattori, Yoshiyuki; Hattori, Sachiko; Akimoto, Kazumi; Nishikimi, Toshio; Suzuki, Kunihiro; Matsuoka, Hiroaki; Kasai, Kikuo

doi:10.2337/db06-1405

Cited by 63 publications

(60 citation statements)

References 24 publications

(21 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, adiponectin had no effect on the proliferation of normal and transformed breast cancer cells and adenocarcinomas (Grossmann et al 2008, Ogunwobi & Beales 2008. Similar results have been obtained with globular adiponectin, with i) growth of epithelial cancer cells, fibroblasts, and hematopoietic stem cells increased (Ogunwobi & Beales 2006, DiMascio et al 2007, Hattori et al 2007; ii) epithelial and breast cancer cells and adenocarcinomas growth inhibited (Fenton et al 2008, Grossmann et al 2008, Ogunwobi & Beales 2008; and iii) growth of normal breast cells and prostate cancer cells unaffected (Grossmann et al 2008, Mistry et al 2008. In studies that directly compared the two forms of adiponectin, both different (breast, prostate, and adenocarcinoma) and similar (epithelial and stem cells) responses have been observed.…”

Section: Discussionsupporting

confidence: 63%

Inhibition of smooth muscle cell proliferation by adiponectin requires proteolytic conversion to its globular form

Fuerst¹,

Taylor²,

Wright³

et al. 2012

Journal of Endocrinology

View full text Add to dashboard Cite

Accelerated atherosclerosis is the primary cardiovascular manifestation of diabetes and correlates inversely with levels of circulating adiponectin, an anti-atherosclerotic adipokine that declines in diabetes. We therefore initiated a study to examine the mechanisms by which adiponectin, a hormone released from adipose tissue, influences the proliferation of vascular smooth muscle cells (SMCs). Addition of adiponectin to quiescent porcine coronary artery SMCs increased both protein and DNA synthesis and concurrently activated ERK1/2 and Akt. By contrast, globular adiponectin, a truncated form of this protein, exhibited anti-mitogenic properties as indicated by the inhibition of protein and DNA synthesis in SMCs stimulated with platelet-derived growth factor (PDGF). Whereas globular adiponectin did not stimulate growth-related signal transduction pathways, it was able to block the PDGF-dependent phosphorylation of eukaryotic elongation factor 2 kinase, a regulator of protein synthesis. Proteolysis of adiponectin with trypsin, which produces globular adiponectin, reversed the growth-stimulating actions of the undigested protein. As the existence of globular adiponectin remains controversial, western blotting was used to establish its presence in rat serum. We found that globular adiponectin was detectable in rat serum, but this result was not obtained with all antibodies. The contrasting properties of adiponectin and its globular form with respect to SMC proliferation suggest that protection against atherosclerosis may therefore be mediated, in part, by the level of globular adiponectin.

show abstract

Section: Discussionsupporting

confidence: 63%

Inhibition of smooth muscle cell proliferation by adiponectin requires proteolytic conversion to its globular form

Fuerst¹,

Taylor²,

Wright³

et al. 2012

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…However, we also showed that higher adiponectin levels could predict HCC risk even after adjustment for all the metabolic variables as well as the liver function-related variables, and most importantly the HBV DNA. Furthermore, it was also documented that adiponectin may have proinflammatory and proproliferative effects in various cell types via the activation of the NFkB, AP-1, and MAPK pathways (48)(49)(50). Therefore, the independent procancerous effect of adiponectin cannot be excluded.…”

Section: Discussionmentioning

confidence: 99%

Plasma Adipokines and Risk of Hepatocellular Carcinoma in Chronic Hepatitis B Virus–Infected Carriers: A Prospective Study in Taiwan

Chen

Yang

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

Background: Obesity is considered a risk factor for hepatocellular carcinoma (HCC). The relationship between adipocytokine and HCC in hepatitis B virus (HBV) carriers remains unclear. We prospectively investigated the association of adiponectin, leptin, and visfatin levels with HCC.Methods: We conducted a nested case-control study in a community-based cohort with 187 incident HCC and 374 HCC-free HBV carriers. Unconditional logistic regression was conducted to estimate the ORs and 95% confidence intervals (CI).Results: Adiponectin, but not leptin and visfatin, levels were associated with an increased risk of HCC after adjustment for other metabolic factors and HBV-related factors. The risk was increased [OR ¼ 0.51; 95% CI, 0.12-2.11; OR ¼ 4.88 (1.46-16.3); OR ¼ 3.79 (1.10-13.0); OR ¼ 4.13 (1.13-15.1) with each additional quintiles, respectively] with a significant dose-response trend (P trend ¼ 0.003). HCC risk associated with higher adiponectin level was higher in HBV carriers with ultrasonographic fatty liver, genotype C infection, higher viral load, and with elevated alanine aminotransferase. Longitudinally, participants with higher adiponectin were less likely to achieve surface antigen of hepatitis B virus (HBsAg) seroclearance and more likely to have persistently higher HBV DNA. Eventually, they were more likely to develop liver cirrhosis [OR ¼ 1.65 (0.62-4.39); OR ¼ 3.85 (1.47-10.1); OR ¼ 2.56 (0.96-6.84); OR ¼ 3.76 (1.33-10.7) for the second, third, fourth, and fifth quintiles, respectively; P trend ¼ 0.017] before HCC.Conclusions: Elevated adiponectin levels were independently associated with an increased risk of HCC. Impact: Adiponectin may play different roles in the virus-induced and metabolic-related liver diseases, but the underlying mechanism remains unknown. Cancer Epidemiol Biomarkers Prev; 23(8); 1659-71. Ó2014 AACR.

show abstract

“…The ERK signaling pathway is activated by adiponectin via AdipoR1/AdipoR2 in keratinocytes MAPK is a well-known factor involved in cell proliferation (39)(40)(41). Akt and AMP-activated protein kinase (AMPK) are also known to enhance cell proliferation and suppress apotosis (10).…”

Section: Adiponectin Induces Keratinocyte Migrationmentioning

confidence: 99%

Adiponectin Regulates Cutaneous Wound Healing by Promoting Keratinocyte Proliferation and Migration via the ERK Signaling Pathway

Shibata

Tada

Asano

et al. 2012

The Journal of Immunology

134

109

View full text Add to dashboard Cite

Diabetic patients are at high risk of developing delayed cutaneous wound healing. Adiponectin plays a pivotal role in the pathogenesis of diabetes and is considered to be involved in various pathological conditions associated with diabetes; however, its role in wound repair is unknown. In this study, we elucidated the involvement of adiponectin in cutaneous wound healing in vitro and in vivo. Normal human keratinocytes expressed adiponectin receptors, and adiponectin enhanced proliferation and migration of keratinocytes in vitro. This proliferative and migratory effect of adiponectin was mediated via AdipoR1/AdipoR2 and the ERK signaling pathway. Consistent with in vitro results, wound closure was significantly delayed in adiponectin-deficient mice compared with wild-type mice, and more importantly, keratinocyte proliferation and migration during wound repair were also impaired in adiponectin-deficient mice. Furthermore, both systemic and topical administration of adiponectin ameliorated impaired wound healing in adiponectin-deficient and diabetic db/db mice, respectively. Collectively, these results indicate that adiponectin is a potent mediator in the regulation of cutaneous wound healing. We propose that upregulation of systemic and/or local adiponectin levels is a potential and very promising therapeutic approach for dealing with diabetic wounds.

show abstract

Globular Adiponectin Activates Nuclear Factor-κB and Activating Protein-1 and Enhances Angiotensin II–Induced Proliferation in Cardiac Fibroblasts

Cited by 63 publications

References 24 publications

Inhibition of smooth muscle cell proliferation by adiponectin requires proteolytic conversion to its globular form

Inhibition of smooth muscle cell proliferation by adiponectin requires proteolytic conversion to its globular form

Plasma Adipokines and Risk of Hepatocellular Carcinoma in Chronic Hepatitis B Virus–Infected Carriers: A Prospective Study in Taiwan

Adiponectin Regulates Cutaneous Wound Healing by Promoting Keratinocyte Proliferation and Migration via the ERK Signaling Pathway

Contact Info

Product

Resources

About