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dc.contributor.authorZhou, Ying
dc.contributor.authorLittle, Peter J
dc.contributor.authorCao, Yingnan
dc.contributor.authorTa, Hang T
dc.contributor.authorKamato, Danielle
dc.date.accessioned2020-09-28T00:52:14Z
dc.date.available2020-09-28T00:52:14Z
dc.date.issued2020
dc.identifier.issn0167-4889
dc.identifier.doi10.1016/j.bbamcr.2020.118848
dc.identifier.urihttp://hdl.handle.net/10072/397966
dc.description.abstractLysophosphatidic acid (LPA) via transactivation dependent signalling pathways contributes to a plethora of physiological and pathophysiological responses. In the vasculature, hyperelongation of glycosaminoglycan (GAG) chains on proteoglycans leads to lipid retention in the intima resulting in the early pathogenesis of atherosclerosis. Therefore, we investigated and defined the contribution of transactivation dependent signalling in LPA mediated GAG chain hyperelongation in human vascular smooth muscle cells (VSMCs). LPA acting via the LPA receptor 5 (LPAR5) transactivates the TGFBR1 to stimulate the mRNA expression of GAG initiation and elongation gene xylosyltransferase-1 (XYLT1) and chondroitin 6-sulfotransferase-1 (CHST3), respectively. We found that LPA stimulates ROS and Akt signalling in VSMCs, however they are not associated in LPAR5 mediated transactivation of the TGFBR1. We observed that LPA via ROCK dependent pathways transactivates the TGFBR1 to stimulate genes associated with GAG chain elongation. We demonstrate that GPCR transactivation of the TGFBR1 occurs via a universal biochemical mechanism and the identified effectors represent potential therapeutic targets to inhibit pathophysiological effects of GPCR transactivation of the TGFBR1.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherElsevier
dc.relation.ispartofpagefrom118848
dc.relation.ispartofissue12
dc.relation.ispartofjournalBiochimica et Biophysica Acta (BBA) - Molecular Cell Research
dc.relation.ispartofvolume1867
dc.subject.fieldofresearchMedical Microbiology
dc.subject.fieldofresearchBiochemistry and Cell Biology
dc.subject.fieldofresearchcode1108
dc.subject.fieldofresearchcode0601
dc.subject.keywordsBiglycan
dc.subject.keywordsG protein-coupled receptor
dc.subject.keywordsKinase receptors
dc.subject.keywordsSmads
dc.subject.keywordsTGF-beta receptor
dc.titleLysophosphatidic acid receptor 5 transactivation of TGFBR1 stimulates the mRNA expression of proteoglycan synthesizing genes XYLT1 and CHST3
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationZhou, Y; Little, PJ; Cao, Y; Ta, HT; Kamato, D, Lysophosphatidic acid receptor 5 transactivation of TGFBR1 stimulates the mRNA expression of proteoglycan synthesizing genes XYLT1 and CHST3, Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2020, 1867 (12), pp. 118848
dcterms.dateAccepted2020-09-03
dc.date.updated2020-09-28T00:40:00Z
gro.hasfulltextNo Full Text
gro.griffith.authorTa, Hang


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