登入
選單
返回
Google圖書搜尋
The Atypical Sphingosine 1-phosphate Variant, D16:1 S1P, Mediates CTGF Induction Via S1P2 Activation in Renal Cell Carcinoma
Melanie Glück
Alexander Koch
Robert Brunkhorst
Nerea Ferreirós Bouzas
Sandra Trautmann
Liliana Schäfer
Waltraud Pfeilschifter
Josef Pfeilschifter
Rajkumar Vutukuri
出版
Wiley-Blackwell
, 2022
URL
http://books.google.com.hk/books?id=FVRk0AEACAAJ&hl=&source=gbs_api
註釋
Sphingosine 1-phosphate (S1P) is a lipid mediator with numerous biological functions. The term 'S1P' mainly refers to the sphingolipid molecule with a long-chain sphingoid base of 18 carbon atoms, d18:1 S1P. The enzyme serine palmitoyltransferase catalyses the first step of the sphingolipid de novo synthesis using palmitoyl-CoA as the main substrate. After further reaction steps, d18:1 S1P is generated. However, also stearyl-CoA or myristoyl-CoA can be utilised by the serine palmitoyltransferase, which at the end of the S1P synthesis pathway, results in the production of d20:1 S1P and d16:1 S1P respectively. We measured these S1P homologues in mice and renal tissue of patients suffering from renal cell carcinoma (RCC). Our experiments highlight the relevance of d16:1 S1P for the induction of connective tissue growth factor (CTGF) in the human renal clear cell carcinoma cell line A498 and human RCC tissue. We show that d16:1 S1P versus d18:1 and d20:1 S1P leads to the highest CTGF induction in A498 cells via S1P2 signalling and that both d16:1 S1P and CTGF levels are elevated in RCC compared to adjacent healthy tissue. Our data indicate that d16:1 S1P modulates conventional S1P signalling by acting as a more potent agonist at the S1P2 receptor than d18:1 S1P. We suggest that elevated plasma levels of d16:1 S1P might play a pro-carcinogenic role in the development of RCC via CTGF induction.