Diabetes in Humans Activates Pancreatic Stellate Cells via RAGE in Pancreatic Ductal Adenocarcinoma.
Diabetes in Humans Activates Pancreatic Stellate Cells via RAGE in Pancreatic Ductal Adenocarcinoma.
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DOI：
10.3390/ijms222111716
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发表时间：
2021-10-28
影响因子：
5.6
通讯作者：
Hakamada K
中科院分区：
文献类型：
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作者：
Uchida C;Mizukami H;Hara Y;Saito T;Umetsu S;Igawa A;Osonoi S;Kudoh K;Yamamoto Y;Yamamoto H;Yagihashi S;Hakamada K
胰腺星形细胞（Pancreatic stellate cells，PSC）主要由胰腺导管腺癌（pancreatic ductal adenocarcinoma，PDAC）的成纤维细胞组成。晚期糖基化终末产物受体（receptor for advanced glycation end products，RECEPTOR）与糖尿病并发症的病理生理学有关。在这里，我们研究了PDAC中的PSC激活中的P450的含义。通过qPCR评估培养的小鼠PSC的活化。在用来自活化PSC的培养上清液刺激下评估PDAC细胞系中上皮间质转化（EMT）的诱导。共155例手术切除的PDAC受试者（83例非糖尿病患者，18例糖尿病病史> 3年，54例糖尿病病史>3年）进行了临床病理学评价。高脂饮食增加了培养的PSC中活化标志物的表达，这是废除了cDNA 3缺失。活化PSC的培养上清促进PDAC细胞的EMT，并增加TGF-β和IL-6，但β-缺失PSC的培养上清则不然。合并代谢综合征的糖尿病受试者，通过聚类分析划分，显示出较高的PSC活化和PSMA表达。在这些组中，PDAC细胞表现出EMT性质。代谢综合征合并糖尿病显著恶化了PDAC受试者的无病生存率。因此，在糖尿病代谢综合征受试者中，PDAC的新启动子和未来的治疗靶点可以被视为一个新的PSCs。
Pancreatic stellate cells (PSCs) mainly consist of cancer-associating fibroblasts in pancreatic ductal adenocarcinoma (PDAC). The receptor for advanced glycation end products (RAGE) is implicated in the pathophysiology of diabetic complications. Here, we studied the implication of RAGE in PSC activation in PDAC. The activation of cultured mouse PSCs was evaluated by qPCR. The induction of epithelial mesenchymal transition (EMT) in PDAC cell lines was assessed under stimulation with culture supernatant from activated PSCs. A total of 155 surgically resected PDAC subjects (83 nondiabetic, 18 with ≦3-years and 54 with >3-years history of diabetes) were clinicopathologically evaluated. A high-fat diet increased the expression of activated markers in cultured PSCs, which was abrogated by RAGE deletion. Culture supernatant from activated PSCs facilitated EMT of PDAC cells with elevation of TGF−β and IL−6, but not from RAGE−deleted PSCs. Diabetic subjects complicated with metabolic syndrome, divided by cluster analysis, showed higher PSC activation and RAGE expression. In such groups, PDAC cells exhibited an EMT nature. The complication of metabolic syndrome with diabetes significantly worsened disease−free survival of PDAC subjects. Thus, RAGE in PSCs can be viewed as a new promoter and a future therapeutic target of PDAC in diabetic subjects with metabolic syndrome.
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影响因子：
29.4
作者：
Apte MV;Wilson JS;Lugea A;Pandol SJ
通讯作者：
Pandol SJ
影响因子：
10.9
作者：
Manigrasso, Michaele B.;Juranek, Judyta;Ramasamy, Ravichandran;Schmidt, Ann Marie
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28.2
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Jain RK
影响因子：
4
作者：
Hong, Oak-Kee;Lee, Seung-Hwan;Yoon, Kun-Ho
通讯作者：
Yoon, Kun-Ho
DOI：
10.1186/s13046-017-0654-6
发表时间：
2018-01-12
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Lee JH;Kim SK;Khawar IA;Jeong SY;Chung S;Kuh HJ
通讯作者：
Kuh HJ