Reticulon 4B (Nogo-B) is necessary for macrophage infiltration and tissue repair

Yu, Jun; Fernández‐Hernando, Carlos; Suárez, Yajaira; Schleicher, Michael; Hao, Zhimin; Wright, Paulette L.; Lorenzo, Annarita Di; Kyriakides, Themis R.; Sessa, William C.

doi:10.1073/pnas.0907359106

Cited by 86 publications

(101 citation statements)

References 36 publications

(37 reference statements)

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“…It is not clear whether the decrease in macrophage recruitment is due to the absence of Nogo-B in the renal epithelium, or in the macrophage itself, where Nogo-B is expressed. 22,24 Other indices of the injury response (such as histological changes, fibrosis, and expression of proinflammatory and profibrotic genes) were not significantly different between WT and Nogo-A/B KO mice (Figures 5C and 6). Possible explanations for this apparent contradiction are that the delay in macrophage recruitment is too transitory to be significant in the overall elaboration of injury, that other compensatory inflammatory stimuli obscure the function of Nogo-B when it is absent, or that the polarization of macrophages in the Nogo-A/B KO animals is different from that in the WT such that a similar amount of tissue injury and fibrosis develops despite overall reduced numbers of macrophages.…”

Section: Discussionmentioning

confidence: 99%

“…Given the marked changes in Nogo-B expression that were observed after UUO, we sought to determine whether WT and Nogo-A/B KO mice displayed differences in this model. Because macrophage infiltration is a major event in the pathophysiology of ureteral obstruction, 20,21 and we have observed changes in leukocyte recruitment to sites of various types of tissue injury in Nogo-A/B KO mice, 22 we assessed whether there were any defects in macrophage recruitment after UUO in Nogo-A/B KO kidneys. There was a significant delay in macrophage recruitment/retention in the obstructed kidney in Nogo-A/B KO mice as compared with WT mice ( Figure 5).…”

Section: Examination Of Renal Parameters In Nogo-a/b Knockout Micementioning

confidence: 99%

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Identification and Regulation of Reticulon 4B (Nogo-B) in Renal Tubular Epithelial Cells

Marin

Moeckel

Al‐Lamki

et al. 2010

The American Journal of Pathology

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Nogo-B is a member of the reticulon family of proteins that has been implicated in diverse forms of vascular injury. Although Nogo-B is expressed in renal tissues, its localization and function in the kidney have not been examined. Here, we report that Nogo-B is expressed specifically in the epithelial cells of the distal nephron segments in the murine kidney. After unilateral ureteral obstruction (UUO) and ischemia/reperfusion, Nogo-B gene and protein levels increased dramatically in the kidney. This increase was driven in part by injury-induced de novo expression in proximal tubules. Examination of Nogo-B immunostaining in human biopsy specimens from patients with acute tubular necrosis showed similar increases in Nogo-B in cortical tubules. Mice genetically deficient in Nogo-A/B were indistinguishable from wild-type (WT) mice based on histological appearance and serum analyses. After UUO, there was a significant delay in recruitment of macrophages to the kidney in the Nogo-A/B-deficient mice. However, measurements of fibrosis, inflammatory gene expression, and histological damage were not significantly different from WT mice. Thus, Nogo-B is highly expressed in murine kidneys in response to experimental injuries and may serve as a marker of diverse forms of renal injury in tissues from mice and humans. Furthermore, Nogo-B may regulate macrophage recruitment after UUO, although it does not greatly affect the degree of tissue injury or fibrosis in this model. (Am J Pathol

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Section: Discussionmentioning

confidence: 99%

Section: Examination Of Renal Parameters In Nogo-a/b Knockout Micementioning

confidence: 99%

Identification and Regulation of Reticulon 4B (Nogo-B) in Renal Tubular Epithelial Cells

Marin

Moeckel

Al‐Lamki

et al. 2010

The American Journal of Pathology

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“…Western blotting analysis using BMM lysates demonstrated the expression of Nogo-B (Fig. 1A, 1C), corresponding to the Nogo-B1 (∼42 kDa) and -B2 (∼46 kDa) isoforms as reported (33,34). In brain tissues, expression of Nogo-A isoform was detectable in both mRNA and protein levels.…”

Section: Nogo-b Is Indispensable For Full Activation Of Nucleic Acidsmentioning

confidence: 93%

Endoplasmic Protein Nogo-B (RTN4-B) Interacts with GRAMD4 and Regulates TLR9-Mediated Innate Immune Responses

Kimura

Endo

Inui

et al. 2015

The Journal of Immunology

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TLRs are distributed in their characteristic cellular or subcellular compartments to efficiently recognize specific ligands and to initiate intracellular signaling. Whereas TLRs recognizing pathogen-associated lipids or proteins are localized to the cell surface, nucleic acid–sensing TLRs are expressed in endosomes and lysosomes. Several endoplasmic reticulum (ER)–resident proteins are known to regulate the trafficking of TLRs to the specific cellular compartments, thus playing important roles in the initiation of innate immune responses. In this study, we show that an ER-resident protein, Nogo-B (or RTN4-B), is necessary for immune responses triggered by nucleic acid–sensing TLRs, and that a newly identified Nogo-B–binding protein (glucosyltransferases, Rab-like GTPase activators and myotubularins [GRAM] domain containing 4 [GRAMD4]) negatively regulates the responses. Production of inflammatory cytokines in vitro by macrophages stimulated with CpG-B oligonucleotides or polyinosinic:polycytidylic acid was attenuated in the absence of Nogo-B, which was also confirmed in serum samples from Nogo-deficient mice injected with polyinosinic:polycytidylic acid. Although a deficiency of Nogo-B did not change the incorporation or delivery of CpG to endosomes, the localization of TLR9 to endolysosomes was found to be impaired. We identified GRAMD4 as a downmodulator for TLR9 response with a Nogo-B binding ability in ER, because our knockdown and overexpression experiments indicated that GRAMD4 suppresses the TLR9 response and knockdown of Gramd4 strongly enhanced the response in the absence of Nogo-B. Our findings indicate a critical role of Nogo-B and GRAMD4 in trafficking of TLR9.

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“…Nogo isoform-B (Nogo-B), also known as reticulon 4B, is a member of the reticulon family [8]. Nogo-B is expressed at high levels in the microvessels [9].…”

Section: Introductionmentioning

confidence: 99%

WITHDRAWN: Endothelial Nogo-B suppresses cancer cell proliferation via a paracrine TGF-β/Smad signaling

Li¹,

Cheng²,

Huang³

et al. 2018

Oncotarget

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Reticulon 4B (Nogo-B) is necessary for macrophage infiltration and tissue repair

Cited by 86 publications

References 36 publications

Identification and Regulation of Reticulon 4B (Nogo-B) in Renal Tubular Epithelial Cells

Identification and Regulation of Reticulon 4B (Nogo-B) in Renal Tubular Epithelial Cells

Endoplasmic Protein Nogo-B (RTN4-B) Interacts with GRAMD4 and Regulates TLR9-Mediated Innate Immune Responses

WITHDRAWN: Endothelial Nogo-B suppresses cancer cell proliferation via a paracrine TGF-β/Smad signaling

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