Progranulin deficiency attenuates tubulointerstitial injury in a mouse unilateral ureteral obstruction model

Eri Adachi ¹, Maki Murakoshi ¹, Terumi Shibata ¹

⁰Department of Nephrology, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.

Experimental Animals +

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February 18, 2024

View abstract on PubMed

Summary

Progranulin (PGRN) deficiency ameliorates kidney tubulointerstitial fibrosis and inflammation. PGRN knockout mice showed reduced fibrosis markers and improved kidney histology after unilateral ureteral obstruction (UUO).

Area Of Science

Nephrology
Immunology
Molecular Biology

Background

Progranulin (PGRN) exhibits dual roles in inflammation, acting both pro- and anti-inflammatory depending on the disease context.
While PGRN's role in liver fibrosis is documented, its specific involvement in tubulointerstitial fibrosis requires further investigation.

Purpose Of The Study

To investigate the role of Progranulin (PGRN) in the pathogenesis of tubulointerstitial fibrosis.
To elucidate the impact of PGRN deficiency on kidney inflammation and fibrosis following unilateral ureteral obstruction (UUO).

Main Methods

Utilized Progranulin-knockout (PGRN-KO) and wild-type (WT) mice subjected to unilateral ureteral obstruction (UUO).
Kidney tissues were analyzed histopathologically and assessed for PGRN protein expression via immunohistochemistry and Western blot.
Quantitative PCR was employed to measure renal mRNA levels of inflammation and fibrosis markers.

Main Results

PGRN-KO mice exhibited significantly improved renal histology, with reduced tubular atrophy, urinary casts, and tubulointerstitial fibrosis compared to WT mice post-UUO.
mRNA expression of key inflammation markers (Il1b, Tnf, Il6, Ccl2, Adgre1) and fibrosis markers (Tgfb1, Acta2, Fn1, Col1a2) were significantly lower in UUO-PGRN-KO mice.
Elevated PGRN and GRN protein levels were observed in the kidneys of UUO-WT mice, correlating with increased renal inflammation and fibrosis.

Conclusions

Progranulin (PGRN) plays a crucial role in promoting renal inflammation and tubulointerstitial fibrosis.
PGRN deficiency confers protection against kidney fibrosis induced by UUO.
Elevated PGRN/GRN levels may contribute to the development of renal inflammation and fibrosis in obstructive nephropathy.

Keywords:

progranulin renal fibrosis unilateral ureteral obstruction model