Role of the high-affinity leukotriene B4 receptor signaling in fibrosis after unilateral ureteral obstruction in mice.
Animals
Apoptosis
/ physiology
Fibroblasts
/ metabolism
Fibrosis
/ metabolism
Kidney
/ metabolism
Kidney Diseases
/ genetics
Kidney Tubules
/ metabolism
Macrophages
/ metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Receptors, Leukotriene B4
/ genetics
Signal Transduction
Ureteral Obstruction
/ genetics
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
05
08
2018
accepted:
10
02
2019
entrez:
1
3
2019
pubmed:
1
3
2019
medline:
4
12
2019
Statut:
epublish
Résumé
Leukotriene B4 (LTB4) is a lipid mediator that acts as a potent chemoattractant for inflammatory leukocytes. Kidney fibrosis is caused by migrating inflammatory cells and kidney-resident cells. Here, we examined the role of the high-affinity LTB4 receptor BLT1 during development of kidney fibrosis induced by unilateral ureteral obstruction (UUO) in wild-type (WT) mice and BLT1 knockout (BLT1-/-) mice. We found elevated expression of 5-lipoxygenase (5-LOX), which generates LTB4, in the renal tubules of UUO kidneys from WT mice and BLT1-/- mice. Accumulation of immunoreactive type I collagen in WT UUO kidneys increased over time; however, the increase was less prominent in BLT1-/- UUO kidneys. Accumulation of S100A4-positive fibroblasts increased temporally in WT UUO kidneys, but was again less pronounced in-BLT1-/- UUO kidneys. The same was true of mRNA encoding transforming growth factor-β (TGF)-β and fibroblast growth factor (FGF)-2. Finally, accumulation of F4/80-positive macrophages, which secrete TGF-β, increased temporally in WT UUO and BLT1-/- UUO kidneys, but to a lesser extent in the latter. Following LTB4 stimulation in vitro, macrophages showed increased expression of mRNA encoding TGF-β/FGF-2 and Col1a1, whereas L929 fibroblasts showed increased expression of mRNA encoding α smooth muscle actin (SMA). Bone marrow (BM) transplantation studies revealed that the area positive for type I collagen was significantly smaller in BLT1-/-BM→WT than in WT-BM→WT. Thus, LTB4-BLT1 signaling plays a critical role in fibrosis in UUO kidneys by increasing accumulation of macrophages and fibroblasts. Therefore, blocking BLT1 may prevent renal fibrosis.
Identifiants
pubmed: 30818366
doi: 10.1371/journal.pone.0202842
pii: PONE-D-18-23121
pmc: PMC6394974
doi:
Substances chimiques
Ltb4r1 protein, mouse
0
Receptors, Leukotriene B4
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0202842Commentaires et corrections
Type : ErratumIn
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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