Fibrinogen-like protein 2 deficiency aggravates renal fibrosis by facilitating macrophage polarization

Wu, Shouzhen; Li, Meng; Xu, Feng; GuiQing, Li; Han, Bo; He, Xiandong; Li, Shujing; He, Qianhui; Lai, Xinyue; Zhou, Shaojun; Zheng, Quan‐you; Guo, Bo; Chen, Jian; Zhang, Ke‐qin; Xu, Guiping

doi:10.1016/j.biopha.2020.110468

Cited by 9 publications

(5 citation statements)

References 36 publications

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“…In a rat model of anti-glomerular basement membrane disease, inhibition of M2 macrophage infiltration by inhibitor of the macrophage-specific c-fms receptor at days 14-35 resulted in a significant reduction in both glomerular sclerosis and interstitial fibrosis (Han et al, 2013). Consistent with findings from experimental animal models, the number of M2 macrophages expressing CD206 and/or CD163 is associated with kidney interstitial fibrosis and tubular atrophy in human kidney diseases such as diabetic nephropathy, IgA nephropathy, and in kidney transplants (Wu et al, 2020). Together these findings indicate that M2 macrophage polarization and infiltration can promote kidney fibrosis and progression of kidney disease.…”

Section: Anti-inflammatory and Pro-fibrotic Roles Of M2 Macrophagessupporting

confidence: 56%

The Role of Macrophages in Kidney Fibrosis

Wang

Chen

et al. 2021

Front. Physiol.

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The phenotypic heterogeneity and functional diversity of macrophages confer on them complexed roles in the development and progression of kidney diseases. After kidney injury, bone marrow-derived monocytes are rapidly recruited to the glomerulus and tubulointerstitium. They are activated and differentiated on site into pro-inflammatory M1 macrophages, which initiate Th1-type adaptive immune responses and damage normal tissues. In contrast, anti-inflammatory M2 macrophages induce Th2-type immune responses, secrete large amounts of TGF-β and anti-inflammatory cytokines, transform into αSMA+ myofibroblasts in injured kidney, inhibit immune responses, and promote wound healing and tissue fibrosis. Previous studies on the role of macrophages in kidney fibrosis were mainly focused on inflammation-associated injury and injury repair. Apart from macrophage-secreted profibrotic cytokines, such as TGF-β, evidence for a direct contribution of macrophages to kidney fibrosis is lacking. However, under inflammatory conditions, Wnt ligands are derived mainly from macrophages and Wnt signaling is central in the network of multiple profibrotic pathways. Largely underinvestigated are the direct contribution of macrophages to profibrotic signaling pathways, macrophage phenotypic heterogeneity and functional diversity in relation to kidney fibrosis, and on their cross-talk with other cells in profibrotic signaling networks that cause fibrosis. Here we aim to provide an overview on the roles of macrophage phenotypic and functional diversity in their contribution to pro-fibrotic signaling pathways, and on the therapeutic potential of targeting macrophages for the treatment of kidney fibrosis.

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Section: Anti-inflammatory and Pro-fibrotic Roles Of M2 Macrophagessupporting

confidence: 56%

The Role of Macrophages in Kidney Fibrosis

Wang

Chen

et al. 2021

Front. Physiol.

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“…Han et al examined the transcription of the hFGL2 gene in response to hepatitis B core (HBc) and hepatitis B virus X protein (HBx) proteins ERK promotes hBC-induced nuclear C-est-2 DNA binding activity and FGL2 induction, while JNK promotes HBX-induced nuclear C-est-2 DNA binding activity and FGL2 induction, ERK and JNK belong to the three core elements of MAPK pathway, thereby MAPK signaling pathway is involved in FGL2 transcription [62]. A recent study showed that the deficiency of FGL2 in a mouse model aggravated UUO-induced renal fibrosis by upregulation STAT6-dependent M2 macrophage polarization [71]. Some researchers discussed that FGL2 can induce the expression levels of CD39 and PD-1, and induce M2 polarization of macrophage [72], and the apoptosis of DC through FcγRIIB pathway [45].…”

Section: Fgl2mentioning

confidence: 99%

The role of Fibrinogen-like proteins in Cancer

Yu¹,

Li²,

Shen³

et al. 2021

Int. J. Biol. Sci.

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Fibrinogen-associated protein (FREP) family is a family of proteins with a fibrin domain at the carboxyl terminus. Recent investigations illustrated that two members of FREP family, fibrinogen-like protein-1 (FGL1) and fibrinogen-like protein-2 (FGL2), play crucial roles in cancer by regulating the proliferation, invasion, and migration of tumor cells, or regulating the functions of immune cells in tumor microenvironment. Meanwhile, they are potential targets for medical intervention of tumor development. In this review, we discussed the structure, and the roles of FGL1 and FGL2 in tumors, especially the roles in regulating immune cell functions.

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“…This is a 439 amino acid protein belonging to the fibrinogen‐related superfamily. It exists as both a type II transmembrane protein found on the surface of macrophages and endothelial cells, and a secreted protein by T cells (Marazzi et al , 1998) and it has been associated with liver, interstitium and renal fibrosis by facilitating macrophage polarization (Foerster et al , 2010; de Ridder et al , 2016; Wu et al , 2020). The membrane bound FGL2 has been shown to possess a serine protease activity, cleaving prothrombin to thrombin leading to fibrin deposition and thrombosis and was originally found to be implicated in the pathogenesis of fulminant hepatitis in humans (Levy et al , 2000) and has been used as a biomarker of severe liver diseases, including cancer (Foerster et al , 2010; Manns et al , 2017; Liu et al , 2021).…”

Section: Discussionmentioning

confidence: 99%

CFTR interactome mapping using the mammalian membrane two‐hybrid high‐throughput screening system

Lim

Snider

Birimberg-Schwartz

et al. 2022

Molecular Systems Biology

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Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a chloride and bicarbonate channel in secretory epithelia with a critical role in maintaining fluid homeostasis. Mutations in CFTR are associated with Cystic Fibrosis (CF), the most common lethal autosomal recessive disorder in Caucasians. While remarkable treatment advances have been made recently in the form of modulator drugs directly rescuing CFTR dysfunction, there is still considerable scope for improvement of therapeutic effectiveness. Here, we report the application of a high-throughput screening variant of the Mammalian Membrane Two-Hybrid (MaMTH-HTS) to map the protein-protein interactions of wild-type (wt) and mutant CFTR (F508del), in an effort to better understand CF cellular effects and identify new drug targets for patient-specific treatments. Combined with functional validation in multiple disease models, we have uncovered candidate proteins with potential roles in CFTR function/CF pathophysiology, including Fibrinogen Like 2 (FGL2), which we demonstrate in patient-derived intestinal organoids has a significant effect on CFTR functional expression.

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Fibrinogen-like protein 2 deficiency aggravates renal fibrosis by facilitating macrophage polarization

Cited by 9 publications

References 36 publications

The Role of Macrophages in Kidney Fibrosis

The Role of Macrophages in Kidney Fibrosis

The role of Fibrinogen-like proteins in Cancer

CFTR interactome mapping using the mammalian membrane two‐hybrid high‐throughput screening system

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