- Miscellaneous
- DN200434 Inhibits Vascular Smooth Muscle Cell Proliferation and Prevents Neointima Formation in Mice after Carotid Artery Ligation
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Sudeep Kumar, Jonghwa Jin, Hyeon Young Park, Mi-Jin Kim, Jungwook Chin, Sungwoo Lee, Jina Kim, Jung-Guk Kim, Yeon-Kyung Choi, Keun-Gyu Park
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Endocrinol Metab. 2022;37(5):800-809. Published online September 28, 2022
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DOI: https://doi.org/10.3803/EnM.2022.1462
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Abstract
PDFPubReader ePub
- Background
Excessive proliferation and migration of vascular smooth muscle cells (VSMCs), which contributes to the development of occlusive vascular diseases, requires elevated mitochondrial oxidative phosphorylation to meet the increased requirements for energy and anabolic precursors. Therefore, therapeutic strategies based on blockade of mitochondrial oxidative phosphorylation are considered promising for treatment of occlusive vascular diseases. Here, we investigated whether DN200434, an orally available estrogen receptor-related gamma inverse agonist, inhibits proliferation and migration of VSMCs and neointima formation by suppressing mitochondrial oxidative phosphorylation.
Methods VSMCs were isolated from the thoracic aortas of 4-week-old Sprague-Dawley rats. Oxidative phosphorylation and the cell cycle were analyzed in fetal bovine serum (FBS)- or platelet-derived growth factor (PDGF)-stimulated VSMCs using a Seahorse XF-24 analyzer and flow cytometry, respectively. A model of neointimal hyperplasia was generated by ligating the left common carotid artery in male C57BL/6J mice.
Results DN200434 inhibited mitochondrial respiration and mammalian target of rapamycin complex 1 activity and consequently suppressed FBS- or PDGF-stimulated proliferation and migration of VSMCs and cell cycle progression. Furthermore, DN200434 reduced carotid artery ligation-induced neointima formation in mice.
Conclusion Our data suggest that DN200434 is a therapeutic option to prevent the progression of atherosclerosis.
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- Jatrorrhizine inhibits Piezo1 activation and reduces vascular inflammation in endothelial cells
Tianying Hong, Xianmei Pan, Han Xu, Zhijuan Zheng, Lizhen Wen, Jing Li, Mingfeng Xia Biomedicine & Pharmacotherapy.2023; 163: 114755. CrossRef
- Lobeglitazone, a Novel Peroxisome Proliferator-Activated Receptor γ Agonist, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice
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Kwi-Hyun Bae, Jung Beom Seo, Yun-A Jung, Hye-Young Seo, Sun Hee Kang, Hui-Jeon Jeon, Jae Man Lee, Sungwoo Lee, Jung-Guk Kim, In-Kyu Lee, Gwon-Soo Jung, Keun-Gyu Park
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Endocrinol Metab. 2017;32(1):115-123. Published online February 28, 2017
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DOI: https://doi.org/10.3803/EnM.2017.32.1.115
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Abstract
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- Background
Renal tubulointerstitial fibrosis is a common feature of the final stage of nearly all cause types of chronic kidney disease. Although classic peroxisome proliferator-activated receptor γ (PPARγ) agonists have a protective effect on diabetic nephropathy, much less is known about their direct effects in renal fibrosis. This study aimed to investigate possible beneficial effects of lobeglitazone, a novel PPARγ agonist, on renal fibrosis in mice. MethodsWe examined the effects of lobeglitazone on renal tubulointerstitial fibrosis in unilateral ureteral obstruction (UUO) induced renal fibrosis mice. We further defined the role of lobeglitazone on transforming growth factor (TGF)-signaling pathways in renal tubulointerstitial fibrosis through in vivo and in vitro study. ResultsThrough hematoxylin/eosin and sirius red staining, we observed that lobeglitazone effectively attenuates UUO-induced renal atrophy and fibrosis. Immunohistochemical analysis in conjunction with quantitative reverse transcription polymerase chain reaction and Western blot analysis revealed that lobeglitazone treatment inhibited UUO-induced upregulation of renal Smad-3 phosphorylation, α-smooth muscle actin, plasminogen activator inhibitor 1, and type 1 collagen. In vitro experiments with rat mesangial cells and NRK-49F renal fibroblast cells suggested that the effects of lobeglitazone on UUO-induced renal fibrosis are mediated by inhibition of the TGF-β/Smad signaling pathway. ConclusionThe present study demonstrates that lobeglitazone has a protective effect on UUO-induced renal fibrosis, suggesting that its clinical applications could extend to the treatment of non-diabetic origin renal disease.
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Citations
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Selikem Nuwormegbe, Na-Young Park, Sun Woong Kim Graefe's Archive for Clinical and Experimental Ophthalmology.2022; 260(1): 149. CrossRef - Comparative Efficacy of Lobeglitazone Versus Pioglitazone on Albuminuria in Patients with Type 2 Diabetes Mellitus
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Jaehyun Bae, Taegyun Park, Hyeyoung Kim, Minyoung Lee, Bong-Soo Cha Diabetes & Metabolism Journal.2021; 45(3): 326. CrossRef - Lobeglitazone, A Peroxisome Proliferator-Activated Receptor-Gamma Agonist, Inhibits Papillary Thyroid Cancer Cell Migration and Invasion by Suppressing p38 MAPK Signaling Pathway
Jun-Qing Jin, Jeong-Sun Han, Jeonghoon Ha, Han-Sang Baek, Dong-Jun Lim Endocrinology and Metabolism.2021; 36(5): 1095. CrossRef - Protocol for a preclinical systematic review and meta-analysis of pharmacological targeting of peroxisome proliferator-activated receptors in experimental renal injury
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