Enhanced glomerular phospholipase activity in the obstructed kidney

Fukuzaki, Atsushi; Morrissey, Jeremiah J.; Klahr, Saulo

doi:10.1007/bf02552148

Cited by 4 publications

(2 citation statements)

References 17 publications

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“…In rat, UUO was shown to increase the activity of a phosphoethanolamine-specific phospholipase A2. 22 The involvement of this enzyme in LPA synthesis in the obstructed kidney remains to be explored.…”

Section: Discussionmentioning

confidence: 99%

LPA1 Receptor Activation Promotes Renal Interstitial Fibrosis

Pradère

Klein²,

Grès

et al. 2007

Journal of the American Society of Nephrology

193

145

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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, the extracellular release of LPA increased approximately 3-fold. Real-time reverse transcription PCR (RT-PCR) analysis demonstrated significant upregulation in the expression of the LPA 1 receptor subtype, downregulation of LPA 3 , and no change of LPA 2 or LPA 4 . TIF was significantly attenuated in LPA 1 (Ϫ/Ϫ) mice compared to wild-type littermates, as measured by expression of collagen III, ␣-smooth muscle actin (␣-SMA), and F4/80. Furthermore, treatment of wild-type mice with the LPA 1 antagonist Ki16425 similarly reduced fibrosis and significantly attenuated renal expression of the profibrotic cytokines connective tissue growth factor (CTGF) and transforming growth factor ␤ (TGF␤). In vitro, LPA induced a rapid, dose-dependent increase in CTGF expression that was inhibited by Ki16425. In conclusion, LPA, likely acting through LPA 1 , is involved in obstruction-induced TIF. Therefore, the LPA 1 receptor might be a pharmaceutical target to treat renal fibrosis.

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Section: Discussionmentioning

confidence: 99%

LPA1 Receptor Activation Promotes Renal Interstitial Fibrosis

Pradère

Klein²,

Grès

et al. 2007

Journal of the American Society of Nephrology

193

145

View full text Add to dashboard Cite

show abstract

“…Preliminary data from our laboratory suggest that neither ATX nor MAGK are responsible for the increased synthesis of LPA associated with renal fibrosis, since their expression is rapidly and strongly down-regulated during UUO (data not shown). In rat, UUO was shown to increase the activity of a phosphoethanolamine-specific PLA2 [65]. The involvement of this enzyme in LPA synthesis in the obstructed kidney remains to be explored.…”

Section: Lpa and Renal Fibrosismentioning

confidence: 98%

Lysophosphatidic acid and renal fibrosis

Pradère

Gonzalez

Klein

et al. 2008

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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HMGB1 exacerbates renal tubulointerstitial fibrosis through facilitating M1 macrophage phenotype at the early stage of obstructive injury

Tian

Zhang

Tang

et al. 2015

American Journal of Physiology-Renal Physiology

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Previous studies have indicated that macrophage phenotype diversity is involved in the progression of renal fibrosis. However, the factors facilitating M1 or M2 phenotypes and the function of these polarized macrophages in kidney injury and fibrosis remain largely unknown. In the present study, we found that macrophages accumulated in the kidney interstitium exhibited mainly as the M1 phenotype at the early stage of unilateral ureter obstruction (UUO). High-mobility group box 1 (HMGB1) protein expressed and released from tubular epithelial cells and interstitial macrophages was essential for the M1 macrophage transition. HMGB1 significantly induced the expression of the M1 marker inducible nitric oxide synthase while decreasing the M2 marker IL-10 in macrophages. Moreover, a glycyrrhizic acid derivative, a blocker of HMGB1 release, reduced UUO-mediated kidney injury and ameliorated UUO-induced renal fibrosis. Interestingly and importantly, UUO caused a low pH value in the urine accumulated in the obstructed ureter, and the acidified urine induced HMGB1 release from tubular epithelial cells and macrophages in vitro. Our data demonstrate that HMGB1 is an essential contributor in facilitating M1 polarization at the early stage of UUO. Inhibition of HMGB1 release may alter macrophage phenotype and contribute to the protection of kidney tissue from injury and fibrosis.

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Enhanced glomerular phospholipase activity in the obstructed kidney

Cited by 4 publications

References 17 publications

LPA1 Receptor Activation Promotes Renal Interstitial Fibrosis

LPA1 Receptor Activation Promotes Renal Interstitial Fibrosis

Lysophosphatidic acid and renal fibrosis

HMGB1 exacerbates renal tubulointerstitial fibrosis through facilitating M1 macrophage phenotype at the early stage of obstructive injury

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