Differential organ-specific inflammatory response to progranulin in high-fat diet-fed mice

Murakoshi, Maki; Gohda, Tomohito; Adachi, Eri; Ichikawa, Saki; Hagiwara, Shinji; Suzuki, Yusuke

doi:10.1038/s41598-020-80940-8

Cited by 8 publications

(5 citation statements)

References 52 publications

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“…In particular, high levels of PGRN inhibit insulin signaling and glucose uptake both in vitro and in vivo and may be involved in the development of obesity-associated insulin resistance, while deficiency of PGRN provides protective action in this condition (41). In addition, our previous study demonstrated that PGRN deficiency exacerbated renal inflammation despite improving systemic inflammation in adipose tissue in mice with HFD-induced obesity (42). Therefore, PGRN may have two absonant effects, depending on the disease stage and tissue microenvironment.…”

Section: Discussionmentioning

confidence: 94%

Progranulin and Its Receptor Predict Kidney Function Decline in Patients With Type 2 Diabetes

et al. 2022

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Progranulin (PGRN), a growth factor, is abundantly expressed in a broad range of tissues and cell types with pleiotropic functions including inflammation, neurodegeneration, and facilitating lysosome acidification. PGRN binds to TNF receptors (TNFR) and inhibits downstream inflammatory signaling pathways. TNFR is a well-known predictor of glomerular filtration rate (GFR) decline in a variety of diseases. Therefore, we measured circulating PGRN in addition to TNFR using an enzyme-linked immunosorbent assay and explored whether it predicted renal prognosis in 201 Japanese patients with type 2 diabetes. During a median follow-up of 7.6 years, 21 participants reached primary renal endpoint, which involves a decline of at least 57% in eGFR from baseline, or the onset of end-stage renal disease. Univariate Cox regression analysis revealed that classical renal measures (GFR and albuminuria), two TNF-related biomarkers (PGRN and TNFR), and BMI were associated with this outcome. Multivariate analysis demonstrated that high levels of PGRN [HR 2.50 (95%CI 2.47–2.52)] or TNFR1 [HR 5.38 (95%CI 5.26–5.50)] were associated with this outcome after adjusting for relevant covariates. The high levels of PGRN as well as TNFR1 were associated with a risk of primary renal outcome in patients with type 2 diabetes after adjusting for established risk factors.

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Section: Discussionmentioning

confidence: 94%

Progranulin and Its Receptor Predict Kidney Function Decline in Patients With Type 2 Diabetes

et al. 2022

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“…Excessive high‐fat food can lead to lipid metabolism disorder, activate the inflammation in the body, and cause inflammatory diseases in various organs (Murakoshi et al., 2021 ). This inflammation can cause the increase in inflammatory factors and attract the invasion of inflammatory cells such as lymphocytes and macrophages (Desai et al., 2017 ; Liu et al., 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Effects of Nostoc sphaeroids Kütz polysaccharide on renal fibrosis in high‐fat mice

Yang

Liu

et al. 2022

Food Science & Nutrition

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In this study, we investigated the effects of Nostoc sphaeroids Kütz polysaccharide (NSKP) on renal fibrosis in high‐fat mice. ApoE−/− male mice were randomly divided into four groups: control (Cont) group, high‐fat diet (HFD) group, HFD+0.4 g/kg BW NSKP, and HFD+0.8 g/kg BW NSKP (NSKP groups). The Cont was fed a standard diet. The HFD group was fed HFD. Every day, NSKP groups were fed HFD, as well as given 0.4 g/kg BW or 0.8 g/kg BW NSKP. After 22 weeks, the serum biochemical indices (TC, TG, LDL‐C, HDL‐C, GLU, BUN, and SCR) were measured. For the kidney, the histopathological sections were observed and analyzed, and inflammatory factors and markers of renal fibrosis were measured. For the NSKP groups, the serum TC, TG, LDL‐C, BUN, and SCR were decreased, HDL‐C significantly increased compared with the HFD group. The protein expressions of TNF‐α, IL‐1β, and TGF‐β1 were significantly downregulated. The α‐SMA in renal cortex was decreased, and the mRNA expression of Col‐I and Col‐IV in renal collagen fibers was downregulated. To sum up, NSKP reduced the blood lipid of HFD mice, downregulated the inflammation of kidney, inhibited the expression of collagen fiber, and improved the renal fibrosis caused by long‐term lipid metabolism disorder.

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“…mRNAs were isolated from the kidney cortex and gene expression was analyzed using qPCR, as described previously [ 13 ]. For total RNA purification, the RNeasy Mini Kit (Qiagen, Hilden, Germany) was used according to the manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

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

Adachi,

Murakoshi,

Shibata

et al. 2024

Exp. Anim.

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Progranulin (PGRN) may have two opposing effects-inflammation and antiinflammation-in different diseases. Although previous studies have reported that PGRN is involved in liver fibrosis, its involvement in tubulointerstitial fibrosis remains to be fully elucidated. Herein, we investigated these issues using PGRN-knockout (KO) mice treated with unilateral ureteral obstruction (UUO). Eight-week-old male PGRN-KO and wild-type (WT) mice were euthanized 3 and 7 days following UUO, and their kidneys were harvested for histopathological analysis. The renal expression of PGRN was evaluated by immunohistochemical and/or western blot analyses. The renal mRNA levels of markers related to inflammation (Il1b, Tnf, Il6, Ccl2, and Adgre1) and fibrosis (Tgfb1, Acta2, Fn1, and Col1a2) were evaluated using quantitative PCR. Histological changes such as renal tubular atrophy, urinary casts, and tubulointerstitial fibrosis were significantly improved in UUO-KO mice compared with UUO-WT mice. Quantitative PCR revealed that the mRNA expression levels of all inflammation-and fibrosis-related markers were lower in UUO-KO mice than in UUO-WT mice at 3 and/or 7 days after UUO. Moreover, PGRN and GRN protein levels were higher in the kidneys of UUO-WT mice than in mice that did not undergo UUO. Elevated GRN levels associated with excess PGRN levels may be involved in the occurrence of renal inflammation and fibrosis in UUO mice.

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Differential organ-specific inflammatory response to progranulin in high-fat diet-fed mice

Cited by 8 publications

References 52 publications

Progranulin and Its Receptor Predict Kidney Function Decline in Patients With Type 2 Diabetes

Progranulin and Its Receptor Predict Kidney Function Decline in Patients With Type 2 Diabetes

Effects of Nostoc sphaeroids Kütz polysaccharide on renal fibrosis in high‐fat mice

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

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