T Helper 2 Cytokine Signaling in Bone Marrow–Derived Fibroblasts

Sakai, Norihiko; Wada, Takashi

doi:10.1681/asn.2015040469

Cited by 9 publications

(6 citation statements)

References 33 publications

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“…MiR‐520a‐3p was revealed to restrain cell proliferation, migration, and invasion by negatively regulating CCND1 and CD44 of breast cancer; in NSCLC, it was also as a suppressor of proliferation, apoptosis, and migration via targeting MAP3K2 (Li et al, ). The JAK/STAT pathway can directly regulate myofibroblast, which means that the JAK/STAT pathway was able to be activated directly in the fibroblasts (Sakai & Wada, ). Besides, the previous evidence presented the role of LIF/JAK/STAT pathway activation in tumor cell growth and differentiation in PTC (J. I.…”

Section: Discussionmentioning

confidence: 99%

Retracted: MicroRNA‐520a‐3p suppresses epithelial–mesenchymal transition, invasion, and migration of papillary thyroid carcinoma cells via the JAK1‐mediated JAK/STAT signaling pathway

Zhang

et al. 2018

Journal Cellular Physiology

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Papillary thyroid cancer (PTC) is a kind of thyroid cancer and frequently presents with epithelial-mesenchymal transition (EMT). MicroRNAs (miRNAs) were previously reported to be associated with PTC. Thus, this study aims to define the role of microRNA-520a-3p (miR-520a-3p) in PTC through the JAK/STAT signaling pathway by targeting JAK1. The PTC and normal thyroid tissues of 137 PTC patients were collected. First of all, the expression pattern of miR-520a-3p, JAK1, JAK2, STAT3, E-cadherin, and vimentin in PTC was identified. The relationship between miR-520a-3p and JAK1 was predicted and analyzed. And a series of miR-520a-3p mimic or inhibitor, or siRNA JAK1 introduced into PTC cells were applied to examine the effect of miR-520a-3p on PTC cell viability, migration, invasion, cell cycle, apoptosis, and EMT. Meanwhile, the regulatory effect of miR-520a-3p and JAK1 on the JAK/STAT signaling pathway was also determined. The expression of JAK1, JAK2, STAT3, and vimentin increased yet miR-520a-3p and E-cadherin decreased in PTC tissue. JAK1 was negatively regulated by miR-520a-3p. Functionally, EMT induction was prevented by miR-520a-3p upregulation through downregulating JAK1. When upregulating miR-520a-3p or silencing JAK1 in PTC cells, PTC cell viability, migration, and invasion were inhibited yet cell apoptosis promoted with cells arrested at G1 phase, indicating that miR-520a-3p prevented PTC progression by downregulating JAK1. Moreover, miR-520a-3p elevation or JAK1 inhibition inactivated the JAK/STAT signaling pathway. Collectively, miR-520a-3p prevents cancer progression through inactivating the JAK/STAT signaling pathway by downregulating JAK1 in PTC.

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Section: Discussionmentioning

confidence: 99%

Retracted: MicroRNA‐520a‐3p suppresses epithelial–mesenchymal transition, invasion, and migration of papillary thyroid carcinoma cells via the JAK1‐mediated JAK/STAT signaling pathway

Zhang

et al. 2018

Journal Cellular Physiology

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“…Accumulating evidence indicates that myeloid myofibroblasts termed fibrocytes play a crucial role in the process of fibrosis ( 4 – 7 ). We and others have previously shown that the recruitment of bone marrow-derived fibroblasts increases the progression and development of renal fibrosis ( 8 – 12 ).…”

Section: Introductionmentioning

confidence: 99%

Pharmacological Inhibition of STAT6 Ameliorates Myeloid Fibroblast Activation and Alternative Macrophage Polarization in Renal Fibrosis

Jiao

Tran

et al. 2021

Front. Immunol.

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A hallmark of chronic kidney disease is renal fibrosis, which can result in progressive loss of kidney function. Currently, there is no effective therapy for renal fibrosis. Therefore, there is an urgent need to identify potential drug targets for renal fibrosis. In this study, we examined the effect of a selective STAT6 inhibitor, AS1517499, on myeloid fibroblast activation, macrophage polarization, and development of renal fibrosis in two experimental murine models. To investigate the effect of STAT6 inhibition on myeloid fibroblast activation, macrophage polarization, and kidney fibrosis, wild-type mice were subjected to unilateral ureteral obstruction or folic acid administration and treated with AS1517499. Mice treated with vehicle were used as control. At the end of experiments, kidneys were harvested for analysis of myeloid fibroblast activation, macrophage polarization, and renal fibrosis and function. Unilateral ureteral obstruction or folic acid administration induced STAT6 activation in interstitial cells of the kidney, which was significantly abolished by AS1517499 treatment. Mice treated with AS1517499 accumulated fewer myeloid fibroblasts and myofibroblasts in the kidney with ureteral obstruction or folic acid nephropathy compared with vehicle-treated mice. Moreover, AS1517499 significantly suppressed M2 macrophage polarization in the injured kidney. Furthermore, AS1517499 markedly reduced the expression levels of extracellular matrix proteins, and development of kidney fibrosis and dysfunction. These findings suggest that AS1517499 inhibits STAT6 activation, suppresses myeloid fibroblast activation, reduces M2 macrophage polarization, attenuates extracellular matrix protein production, and preserves kidney function. Therefore, targeting STAT6 with AS1517499 is a novel therapeutic approach for chronic kidney disease.

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“…Recently, mounting evidence indicates that bone marrow-derived fibroblast precursors contribute significantly to the population of activated fibroblasts and the development of renal fibrosis 7–10 . Bone marrow-derived fibroblast precursors termed fibrocytes are spindle-shaped cells that express hematopoietic markers such as CD45 and CD11b as well as mesenchymal markers such as platelet-derived growth factor receptor-β (PDGFR-β) and vimentin 11–13 .…”

Section: Introductionmentioning

confidence: 99%

The IL-4 receptor α has a critical role in bone marrow–derived fibroblast activation and renal fibrosis

Liu

Zhang

Yan

et al. 2017

Kidney International

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Renal fibrosis is a common pathway leading to the progression of chronic kidney disease and bone marrow derived fibroblasts contribute significantly to the development of renal fibrosis. However, the signaling mechanisms underlying the activation of these fibroblasts are not completely understood. Here, we examined the role of IL-4 receptor α (IL-4Rα) in the activation of myeloid fibroblasts in two experimental models of renal fibrosis. Compared with wild-type mice, IL-4Rα knockout mice accumulated fewer bone marrow derived fibroblasts and myofibroblasts in their kidneys. IL-4Rα deficiency suppressed the expression of α-smooth muscle actin, extracellular matrix proteins and the development of renal fibrosis. Furthermore, IL-4Rα deficiency inhibited the activation of signal transducer and activator of transcription 6 (STAT6) in the kidney. Moreover, wild-type mice engrafted with bone marrow cells from IL-4Rα knockout mice exhibited fewer myeloid fibroblasts in the kidney and displayed less severe renal fibrosis following ureteral obstructive injury compared with wild-type mice engrafted with wild-type bone marrow cells. In vitro, IL-4 activated STAT6 and stimulated expression of α-smooth muscle actin and fibronectin in mouse bone marrow monocytes. This was abolished in the absence of IL-4Rα. Thus, IL-4Rα plays an important role in bone marrow-derived fibroblast activation resulting in extracellular matrix protein production and fibrosis development. Hence, the IL-4Rα/STAT6 signaling pathway may serve as a novel therapeutic target for chronic kidney disease.

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T Helper 2 Cytokine Signaling in Bone Marrow–Derived Fibroblasts

Cited by 9 publications

References 33 publications

Retracted: MicroRNA‐520a‐3p suppresses epithelial–mesenchymal transition, invasion, and migration of papillary thyroid carcinoma cells via the JAK1‐mediated JAK/STAT signaling pathway

Retracted: MicroRNA‐520a‐3p suppresses epithelial–mesenchymal transition, invasion, and migration of papillary thyroid carcinoma cells via the JAK1‐mediated JAK/STAT signaling pathway

Pharmacological Inhibition of STAT6 Ameliorates Myeloid Fibroblast Activation and Alternative Macrophage Polarization in Renal Fibrosis

The IL-4 receptor α has a critical role in bone marrow–derived fibroblast activation and renal fibrosis

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