The c(RGDyK)-Conjugated Fe&lt;SUB&gt;3&lt;/SUB&gt;O&lt;SUB&gt;4&lt;/SUB&gt; Nanoparticles with High Drug Load for Dual-Targeting Integrin &lt;I&gt;α&lt;/I&gt;&lt;SUB&gt;v&lt;/SUB&gt;&lt;I&gt;β&lt;/I&gt;&lt;SUB&gt;3&lt;/SUB&gt;-Expressing Cancer Cells

Guo, Lin; Ding, Wence; Zheng, Li‐Min

doi:10.1166/jnn.2014.8691

Cited by 7 publications

(3 citation statements)

References 17 publications

(18 reference statements)

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“…In the presence of control RGD peptide, irisin raised the mRNA level of sclerostin, while these inhibitors all prevented sclerostin induction. We also injected the irisin peptide into wild-type mice, in combination with control RGD peptide or cyclo RGDyK, an integrin inhibitor that is widely used for in vivo studies (Chen et al, 2004; Guo et al, 2014) (Figure 6D-E). Cyclo RGDyK prevented the irisin-induced gene expression of sclerostin in osteocyte-enriched bones, as well as the protein level in plasma.…”

Section: Introductionmentioning

confidence: 99%

Irisin Mediates Effects on Bone and Fat via αV Integrin Receptors

Kim

Wrann²,

Jedrychowski

et al. 2018

Cell

447

431

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Summary Irisin is secreted by muscle, increased with exercise and mediates certain favorable effects of physical activity. In particular, irisin has been shown to have beneficial effects in adipose tissues, brain and bone. However, the skeletal response to exercise is less clear and the receptor for irisin has not been identified. Here we show that irisin binds to proteins of the αV class of integrins and biophysical studies identify interacting surfaces between irisin and αV/β5 integrin. Chemical inhibition of the αV integrins blocks signaling and function by irisin in osteocytes and fat cells. Irisin increases both osteocytic survival and production of sclerostin, a local modulator of bone remodeling. Genetic ablation of FNDC5/irisin completely blocks osteocytic osteolysis induced by ovariectomy, preventing bone loss and supporting an important role for irisin in skeletal remodeling. The identification of the irisin receptor should greatly facilitate our understanding of irisin’s function in exercise and human health.

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Section: Introductionmentioning

confidence: 99%

Irisin Mediates Effects on Bone and Fat via αV Integrin Receptors

Kim

Wrann²,

Jedrychowski

et al. 2018

Cell

447

431

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show abstract

“…The diabetic rats were allocated to four groups: sedentary diabetic (DM), sedentary diabetic treated intraperitoneally with 1 mg/kg of αV integrin receptor inhibitor 7 (CycloRGDyK - S7844, Selleck Chemicals®, Houston, TX, USA) five days a week (DM + CycloRGDyK), diabetic exercised animals (DM + Exe), and diabetic exercised rats treated intraperitoneally with 1 mg/kg of CycloRGDyK five days a week (DM + Exe + CycloRGDyK) for eight weeks (Supplementary Figure 1 B). CycloRGDyK is a specific inhibitor for integrin class 23 , 24 , that is widely used in vivo studies 25 , 26 .…”

Section: Methodsmentioning

confidence: 99%

Renal protection induced by physical exercise may be mediated by the irisin/AMPK axis in diabetic nephropathy

Formigari

Dátilo

Vareda

et al. 2022

Sci Rep

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In patients with diabetes, it has been suggested that physical exercise may reduce albuminuria and the progression of renal disease. However, the molecular mechanism by which physical exercise protects the kidney in diabetes remains poorly understood. The aim of the present study was to determine the contribution of muscle irisin secretion induced by aerobic physical exercise with the subsequent activation of AMPK for kidney protection under diabetic conditions. Aerobic physical exercise in rats protected the kidney in streptozotocin-induced diabetes. It reduced albuminuria, glomerular hypertrophy, and glomerular expression of collagen IV and fibronectin, as well as markers of kidney inflammation, when compared to sedentary diabetic rats. These effects were associated with elevation in muscle FNDC5/irisin and activity of AMPK in the diabetic kidney. However, the beneficial effects of exercise were lost when the diabetic rats were treated with CycloRGDyK, that in the bone it has been described as an irisin receptor blocker. In cultured human tubular (HK-2) cells, treatment with recombinant irisin counteracted the effect of high glucose in a dose-dependent manner. Irisin, per se, also activated AMPK in HK-2 cells. It is concluded that in diabetes, the renal protective effect of exercise may be mediated by the irisin/AMPK pathway.

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“…c(RGDyK) (molecular weight, 619.51) was synthesized by GL Biochem Ltd. (Shanghai, China). Liposomes loaded with doxorubicin and c(RGDyK)-L-[CD] were prepared in our lab using the method described previously (20). Doxorubicin (1 ml) diluted in PBS was added into a dialysis bag.…”

Section: Methodsmentioning

confidence: 99%

miR‑21 inhibitor facilitates the anticancer activity of doxorubicin loaded nanometer in melanoma

et al. 2019

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) is a potential therapeutic target for melanoma. Whether miR-21 inhibitor affects the anti-cancer activity of doxorubicin assisted by c(RGDyK)-modified liposome (DLN) in melanoma and the underlying mechanisms are largely unknown. In this study, in vitro and animal models were used to explore the effect of DLN combined with miR-21 inhibitor on melanoma cells. The data demonstrated that treatment with 5 µl DLN (final concentration of doxorubicin 5 mg/ml) for 72 h effectively inhibited melanoma cell growth (~75% inhibition). The experiments were then divided into five groups: Control group, vector group, DLN group, miR-21 inhibitor group and miR-21 inhibitor + DLN group. Compared with the control group, DLN (5 µl) or miR-21 inhibitor significantly reduced migration and invasion of melanoma cells, promoted apoptosis and arrested cells at the G1 phase. Notably, the combined application of DLN with miR-21 inhibitor further promoted the anti-cancer effects (reducing migration and invasion of melanoma cells, promoting apoptosis and arresting cells at G1 phase) compared with individual application of DLN or miR-21 inhibitor. Mechanically, DLN did not function by reducing miR-21 expression, whereas DLN and miR-21 inhibitor downregulated B-cell lymphoma-2 (BCL-2) expression, and facilitated BCL-2-associated X protein (Bax) and P53 expression in melanoma cells. DLN and miR-21 inhibitor together displayed stronger effects on Bcl-2, Bax and P53 expression that each alone. In vivo data further demonstrated that DLN inhibited tumor growth further than a similar dose of doxorubicin only. Furthermore, miR-21 inhibitor and DLN exerted the optimal anti-cancer effect compared with single application of DLN or miR-21 inhibitor. Together, the findings demonstrated miR-21 inhibitor facilitated the anti-cancer activity of DLN in melanoma, and the mechanisms involved Bcl-2, Bax and P53 expression.

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The c(RGDyK)-Conjugated Fe<SUB>3</SUB>O<SUB>4</SUB> Nanoparticles with High Drug Load for Dual-Targeting Integrin <I>α</I><SUB>v</SUB><I>β</I><SUB>3</SUB>-Expressing Cancer Cells

Cited by 7 publications

References 17 publications

Irisin Mediates Effects on Bone and Fat via αV Integrin Receptors

Irisin Mediates Effects on Bone and Fat via αV Integrin Receptors

Renal protection induced by physical exercise may be mediated by the irisin/AMPK axis in diabetic nephropathy

miR‑21 inhibitor facilitates the anticancer activity of doxorubicin loaded nanometer in melanoma

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