Deletion of progranulin exacerbates atherosclerosis in ApoE knockout mice

Kawase, Ryota; Ohama, Tohru; Matsuyama, Akifumi; Matsuwaki, Takashi; Okada, Takeshi; Yamashita, Toru; Yuasa-Kawase, Miyako; Nakaoka, Hajime; Nakatani, Kazuhiro; Inagaki, Miwako; Tsubakio-Yamamoto, Kazumi; Masuda, Daisuke; Nakagawa-Toyama, Yumiko; Nishida, Makoto; Ohmoto, Yasukazu; Nishihara, Masugi; Komuro, Issei; Yamashita, Shizuya

doi:10.1093/cvr/cvt178

Cited by 73 publications

(63 citation statements)

References 28 publications

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“…Indeed, others have reported that deletion of progranulin increases macrophage CD36 expression and induces local inflammation. 73 Several studies have linked progranulin activity with IL-6 expression; 74, 75 however, we are unaware of previous work linking progranulin deficiency and increased expression of CD126, a receptor of IL-6. As expected from previous work, wt microglia MHC class II expression was increased following BMT, 48 and this effect was equivalent in wt and Grn −/− BMT recipients.…”

Section: Discussionmentioning

confidence: 99%

Wild-type bone marrow transplant partially reverses neuroinflammation in progranulin-deficient mice

Yang

Aloi

Cudaback

et al. 2014

Laboratory Investigation

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Frontotemporal dementia (FTD) is a neurodegenerative disease with devastating changes in behavioral performance and social function. Mutations in the progranulin gene (GRN) are one of the most common causes of inherited FTD due to reduced progranulin expression or activity, including in brain where it is expressed primarily by neurons and microglia. Thus, efforts aimed at enhancing progranulin levels might be a promising therapeutic strategy. Bone marrow-derived cells are able to engraft in the brain and adopt a microglial phenotype under myeloablative irradiation conditioning. This ability makes bone marrow (BM)-derived cells a potential cellular vehicle for transferring therapeutic molecules to the central nervous system. Here, we utilized BM cells from Grn+/+ (wild type or wt) mice labeled with green fluorescence protein for delivery of progranulin to progranulin deficient (Grn−/−) mice. Our results showed that wt bone marrow transplantation (BMT) partially reconstituted progranulin in the periphery and in cerebral cortex of Grn−/− mice. We demonstrated a pro-inflammatory effect in vivo and in ex vivo preparations of cerebral cortex of Grn−/− mice that was partially to fully reversed five months after BMT. Our findings suggest that BMT can be administered as a stem cell-based approach to prevent or to treat neurodegenerative diseases.

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Section: Discussionmentioning

confidence: 99%

Wild-type bone marrow transplant partially reverses neuroinflammation in progranulin-deficient mice

Yang

Aloi

Cudaback

et al. 2014

Laboratory Investigation

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“…PGRN plays a critical role in various physiological processes, including early embryogenesis, wound healing, and host defense responses. PGRN is also widely involved in the pathogenesis of many diseases, including autoimmune disorders, atherosclerosis, and cancer [19][20][21]. Recent studies have highlighted the important role of PGRN in inflammatory responses and diseases.…”

Section: Introductionmentioning

confidence: 99%

Progranulin protects against endotoxin-induced acute kidney injury by downregulating renal cell death and inflammatory responses in mice

Gou

Zhou

et al. 2016

International Immunopharmacology

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“…PGRN-mediated inhibition of TNFα activity has been well established [11; 12; 13; 14; 15; 16; 17; 18; 19]. For instance, PGRN diminishes TNFα-trigged production of reactive oxygen species in neutrophils [11].…”

Section: Introductionmentioning

confidence: 99%

Three TNFR-binding domains of PGRN act independently in inhibition of TNF-alpha binding and activity

et al. 2014

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PGRN was previously reported to bind to TNF receptors (TNFR) and is therapeutic against inflammatory arthritis. Here we present further evidences demonstrating the PGRN inhibition of TNFα binding and activity, and clarifying the distinct mechanisms underlying TNFα inhibition between PGRN and classic TNFα-binding inhibitors. In addition, we present evidences indicating that three TNFR binding domains of PGRN act independently in binding to TNFR. Furthermore, changing the order of three TNFR-binding domains in Atsttrin, an PGRN-derived molecule composed of these TNFR-binding domains, does not affect its anti-inflammatory and anti-TNF activities in both collagen-induced inflammatory arthritis and human TNF-α transgenic mouse model. Taken together, these findings provide the additional molecular basis underlying PGRN/TNFR interaction and PGRN-mediated anti-inflammatory activity in various inflammatory diseases and conditions.

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Deletion of progranulin exacerbates atherosclerosis in ApoE knockout mice

Abstract: PGRN seems to be involved in the pathogenesis of atherosclerosis, possibly by various anti-atherogenic effects, including modulation of local and/or systemic inflammation.

Cited by 73 publications

References 28 publications

Wild-type bone marrow transplant partially reverses neuroinflammation in progranulin-deficient mice

Wild-type bone marrow transplant partially reverses neuroinflammation in progranulin-deficient mice

Progranulin protects against endotoxin-induced acute kidney injury by downregulating renal cell death and inflammatory responses in mice

Three TNFR-binding domains of PGRN act independently in inhibition of TNF-alpha binding and activity

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