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Identification of the Source of Secreted Proteins in the Kidney by Brefeldin A Injection
Published on: November 10, 2021
PGD2-CRTH2 pathway promotes tubulointerstitial fibrosis
Hideyuki Ito1, Xiaoxiang Yan, Nanae Nagata
1Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. hideyuki.ito@jikei.ac.jp
Journal of the American Society of Nephrology : JASN
|September 22, 2012
Summary
Lipocalin-type PGD(2) synthase (L-PGDS) drives kidney fibrosis by activating Th2 lymphocytes via CRTH2. Blocking this pathway, using CRTH2 antagonists, significantly reduces renal fibrosis progression in mouse models of chronic kidney disease.
Area of Science:
- Nephrology
- Immunology
- Biochemistry
Background:
- Urinary lipocalin-type PGD(2) synthase (L-PGDS) increases in early diabetic nephropathy.
- Increased L-PGDS expression in tubular epithelium suggests a role in chronic kidney disease (CKD) development.
Purpose of the Study:
- To investigate the role of L-PGDS-derived PGD(2) in renal fibrosis progression.
- To explore the mechanism involving CRTH2-mediated Th2 lymphocyte activation.
Main Methods:
- Utilized a unilateral ureteral obstruction (UUO) mouse model.
- Generated L-PGDS-knockout and CRTH2-knockout mice.
- Administered a CRTH2 antagonist and evaluated IL-4/IL-13 ablation effects.
Main Results:
- L-PGDS-knockout and CRTH2-knockout mice showed reduced renal fibrosis and Th2 lymphocyte infiltration.
- CRTH2 antagonist treatment suppressed renal fibrosis progression post-UUO.
- Ablation of IL-4 and IL-13 ameliorated renal fibrosis in UUO kidneys.
Conclusions:
- L-PGDS-derived PGD(2) contributes to renal fibrosis via CRTH2-mediated Th2 activation.
- Blocking CRTH2 activation by PGD(2) is a potential therapeutic strategy for CKD.
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