2007
DOI: 10.1681/asn.2007020196
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LPA1 Receptor Activation Promotes Renal Interstitial Fibrosis

Abstract: Tubulointerstitial fibrosis in chronic renal disease is strongly associated with progressive loss of renal function. We studied the potential involvement of lysophosphatidic acid (LPA), a growth factor-like phospholipid, and its receptors LPA 1-4 in the development of tubulointerstitial fibrosis (TIF). Renal fibrosis was induced in mice by unilateral ureteral obstruction (UUO) for up to 8 d, and kidney explants were prepared from the distal poles to measure LPA release into conditioned media. After obstruction… Show more

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Cited by 193 publications
(155 citation statements)
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“…Mouse model studies have revealed an important role for the ATX-LPA receptor axis in tumor progression as well as in other pathologies, ranging from inflammation to fibrosis (2,(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). Accordingly, pharmacological inhibition of ATX is an attractive way to interfere with LPA signaling for therapeutic benefit.…”
Section: Discussionmentioning
confidence: 99%
“…Mouse model studies have revealed an important role for the ATX-LPA receptor axis in tumor progression as well as in other pathologies, ranging from inflammation to fibrosis (2,(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). Accordingly, pharmacological inhibition of ATX is an attractive way to interfere with LPA signaling for therapeutic benefit.…”
Section: Discussionmentioning
confidence: 99%
“…The available pharmacological tools targeting ATX/LPA signalling are still scarce [7][8][9]. Ki16425 [10] is a mixed LPA receptor antagonist that exhibits close and preferential affinity for the LPA1R and LPA3R subtypes (250 and 360 nmol/l, respectively) [8,10] and its in vivo antagonist efficiency has been documented [11][12][13].…”
Section: Introductionmentioning
confidence: 99%
“…White adipose tissue secretes ATX and LPA in the extracellular milieu [12,[14][15][16]. The expression of ATX is increased in the adipose tissue of obese insulin-resistant individuals and mice [16][17][18].…”
Section: Introductionmentioning
confidence: 99%
“…Des études réalisées chez des patients atteints de maladies rénales chroniques ont démontré une augmentation de la concentration plasmatique de ce phospholipide [31]. De plus, il a été montré que le LPA induisait la synthèse et la sécrétion de CTGF par les fibroblastes interstitiels et les cellules épithéliales tubulaires in vitro (Figure 3) [31,32] et que le blocage de son action in vivo réduisait fortement la progression de la FTI [32].…”
Section: Mécanismes De Progression De La Fibrose : Un Tableau Toujourunclassified