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http://ir.nhri.org.tw/handle/3990099045/12881
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| Title: | Endothelin-1 stimulates preadipocyte growth via the PKC, STAT3, AMPK, c-JUN, ERK, sphingosine kinase, and sphingomyelinase pathways |
| Authors: | Siao, AC;Lin, YY;Shih, LJ;Tsuei, YW;Chuu, CP;Kuo, YC;Kao, YH |
| Contributors: | Institute of Cellular and Systems Medicine |
| Abstract: | Endothelin (ET)-1 regulates adipogenesis and the endocrine activity of fat cells. However, relatively little is known about the ET-1 signaling pathway in preadipocyte growth. We used 3T3-L1 preadipocytes to investigate the signaling pathways involved in ET-1 modulation of preadipocyte proliferation. As indicated by an increased number of cells and greater incorporation of BrdU, the stimulation of preadipocyte growth by ET-1 depends on concentration and timing. The concentration of ET-1 that increased preadipocyte number by 50-70% was approximately 100 nM for approximately 24-48 h of treatment. ET-1 signaling time-dependently stimulated phosphorylation of ERK, c-JUN, STAT3, AMPK, and PKCα/βII proteins, but not AKT, JNK, or p38 MAPK. Treatment with an ET(A)R antagonist, such as BQ610, but not ET(B)R antagonist BQ788, blocked the ET-1-induced increase in cell proliferation and phosphorylated levels of ERK, c-JUN, STAT3, AMPK, and PKCα/βII proteins. In addition, pretreatment with specific inhibitors of ERK1/2 (U0126), JNK (SP600125), JAK2/STAT-3 (AG490), AMPK (Compound C), or PKC (Ro318220) prevented the ET-1-induced increase in cell proliferation and reduced the ET-1-stimulated phosphorylation of ERK1/2, c-JUN, STAT-3, AMPK, and PKCα/β. Moreover, SphK antagonist suppressed ET-1-induced cell proliferation and ERK, c-JUN, STAT3, AMPK, and PKC phosphorylation, and SMase2 antagonist suppressed ET-1-induced cell proliferation. However, neither p38 MAPK antagonist nor CerS inhibitor altered the effect of ET-1. The results indicate that ET(A)R, JAK2/STAT3, ERK1/2, JNK/c-JUN, AMPK, PKC, SphK, and SMase2, but not ET(B)R, p38 MAPK, or CerS, are necessary for the ET-1 stimulation of preadipocyte proliferation. |
| Date: | 2020-11 |
| Relation: | American Journal of Physiology. Cell Physiology. 2020 Nov;319(5):C839-C857. |
| Link to: | http://dx.doi.org/10.1152/ajpcell.00491.2019 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0363-6143&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000581601600005 |
| Cited Times(Scopus): | https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85092944469 |
| Appears in Collections: | [褚志斌] 期刊論文
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| PUB32755450.pdf | | 11589Kb | Adobe PDF | 261 | View/Open |
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