Author(s): Jang MW, Yun SP, Park JH,Ryu JM, Lee JH, et al.
Prostaglandin E(2) (PGE(2)) is well known to regulate cell functions through cAMP; however, the role of exchange protein directly activated by cAMP (Epac1) and protein kinase A (PKA) in modulating such functions is unknown in human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs). Therefore, we investigated the relationship between Epac1 and PKA during PGE(2)-induced hUCB-MSC proliferation and its related signaling pathways. PGE(2) increased cell proliferation, and E-type prostaglandin (EP) 2 receptor mRNA expression level and activated cAMP generation, which were blocked by EP2 receptor selective antagonist AH 6809. PGE(2) increased Epac1 expression, Ras-related protein 1 (Rap1) activation level, and Akt phosphorylation, which were inhibited by AH 6809, adenylyl cyclase inhibitor SQ 22536, and Epac1/Rap1-specific siRNA. Also, PGE(2) increased PKA activity, which was inhibited by AH 6809, SQ 22536, and PKA inhibitor PKI. HUCB-MSCs were incubated with the Epac agonist 8-pCPT-cAMP or the PKA agonist 6-phe-cAMP to examine whether Epac1/Rap1/Akt activation was independent of PKA activation. 8-pCPT-cAMP increased Akt phosphorylation but not PKA activity. 6-Phe-cAMP increased PKA activity, but not Akt phosphorylation. Additionally, an Akt inhibitor or PKA inhibitor (PKI) did not block the PGE(2) -induced increase in PKA activity or Akt phosphorylation, respectively. Moreover, PGE(2) increased glycogen synthase kinase (GSK)-3β phosphorylation and nuclear translocation of active-β-catenin, which were inhibited by Akt inhibitor or/and PKI. PGE(2) increased c-Myc and vascular endothelial growth factor (VEGF) expression levels, which were blocked by β-catenin siRNA. In conclusion, PGE(2) stimulated hUCB-MSC proliferation through β-catenin-mediated c-Myc and VEGF expression via Epac/Rap1/Akt and PKA cooperation.
Referred From: https://www.ncbi.nlm.nih.gov/pubmed/22378492
Author(s): Kitayama H, Matsuzaki T, Ikawa Y, Noda M
Author(s): Sebzda E, Bracke M, TugalT
Author(s): Duchniewicz M, Zwartkruis T, Kolanczyk M
Author(s): Minato N, Katagiri.K, Hattori M
Author(s): Chrzanowska-Wodnicka M, Gale D, White GC, Vansluys J
Author(s): Carmona G, Göttig S, Orlandi A, Scheele J, Bäuerle T, et al
Author(s): Chen Y, Yu M, Podd A, Wen R, Chrzanowska-Wodnicka M, et al.
Author(s): Li Y, Yan J, De P, Chang HC, Yamauchi A, et al.
Author(s): Yan J, Ingram DA, Qilliam LA
Author(s): Hitchcock IS, Kaushansky K
Author(s): Awasthi A, Samarakoon A, Chu H,Kamalakannan R, Quilliam LA, et al.
Author(s): Ghandour H, Cullere X, Alvarez A , Luscinskas FW, Mayadas TN
Author(s): Shimonaka M, Nakayama T, Fujita N, Katagiri K, Tsuruo T, et al.
Author(s): Satyanarayana A, Gudmundsson KO, Chen X, Coppola V, Tessarollo L, et al.
Author(s): Carmona G, Chavakis E, Koehl U, Zeiher AM, Dimmeler S
Author(s): Molina-Ortiz P, Polizzi S, Ramery E, Gayral S, Delierneux C, et al.
Author(s): Karp JM, LengTeo GS
Author(s): Thankamony SP, Sackstein R
Author(s): Chen CP, Huang JP, Chu TY, Aplin JD, Chen CY, et al.
Author(s): Dorn A, Zoellner A, Follo M, Martin S, Weber F, et al.
Author(s): Antignano F, Burrows K, Hughes MR, Han JM, Kron KJ, et al.
Author(s): Zhang X, Cook PC, Zindy E, Williams CJ, Jowitt TA, et al.
Author(s): Tachibana M, Sugimoto K, Nozaki M, Ueda J, Ohta T, et al.
Author(s): Zhang T, Termanis A, Özkan B, Bao XX, Culley J, et al.