Is the Macrophage Phenotype Determinant for Fibrosis Development?

Lis-López, L; Bauset, C; Seco-Cervera, Marta; Cosín-Roger, Jesús

doi:10.3390/biomedicines9121747

Cited by 45 publications

(38 citation statements)

References 188 publications

(270 reference statements)

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“…Macrophages are immune cells implicated in the innate immune response, and they perform different functions, including the inflammatory process, wound healing and fibrosis [8,9]. The different functions arise from the way macrophages change their phenotype and release a variety of biological mediators depending on their surroundings.…”

Section: Introductionmentioning

confidence: 99%

IFNγ-Treated Macrophages Induce EMT through the WNT Pathway: Relevance in Crohn’s Disease

et al. 2022

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Background: Fibrosis is a common complication of Crohn’s disease (CD) in which macrophages play a central role. Epithelial-mesenchymal transition (EMT) and the WNT pathway have been associated with fibrosis. We aim to analyse the relevance of the tissue microenvironment in macrophage phenotype and the EMT process. Methods: Intestinal surgical resections are obtained from control and CD patients with stenotic or penetrating behaviour. Cytokine’s expression, macrophage phenotype, EMT markers and WNT signalling pathway are determined by WB, RT-PCR, ELISA or Cytometry. U937 cells are treated with IFNγ, TNFα, IL1β, IL4 or IL10 and co-cultured with HT29 cells and, in some cases, are treated with XAV939 or miFZD4. The expression of macrophage, EMT and WNT pathway markers in U937 or HT29 cells is analysed by WB or RT-PCR. Results: IFNγ, WNT6, CD16 and CD86 are increased in the intestinal tissue of CD patients. IFNγ-treated U937 activated the EMT process and WNT pathway in HT29 cells, and the EMT process is mediated by FZD4. Conclusions: An IFNγ-rich microenvironment polarises macrophages, which induces EMT through the WNT pathway.

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Section: Introductionmentioning

confidence: 99%

IFNγ-Treated Macrophages Induce EMT through the WNT Pathway: Relevance in Crohn’s Disease

et al. 2022

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“…The presence of M2 macrophages is necessary to resolve inflammation and begin the process of tissue remodeling. 37 However, a persistent presence of M2 macrophages can predispose tissue to the formation of fibrosis. 38 By altering or skewing the polarization state of macrophages to a more favorable state, such as reducing the amount of M2 macrophages, the fibrotic response could be reduced.…”

Section: Discussionmentioning

confidence: 99%

Wound Healing Response After Bleb-Forming Glaucoma Surgery With a SIBS Microshunt in Rabbits

Mechelen

Wolters

Herfs

et al. 2022

Trans. Vis. Sci. Tech.

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Purpose The PreserFlo MicroShunt is an innovative implant for the surgical treatment of glaucoma. Although usually effective, surgeries can still fail due to fibrosis. This study was conducted to gain insight into the histological aspects of the fibrotic response and find potential targets to reduce postoperative fibrosis. Methods Fifteen New Zealand White rabbits were implanted with a microshunt and followed up for 40 days. Animals were euthanized at postoperative days (PODs) 1, 5, and 40 to collect eyes for histological evaluation. Bleb formation and ocular health were assessed by slit-lamp (SL) biomicroscopy and optical coherence tomography (OCT). Intraocular pressure (IOP) was measured using rebound tonometry. Results Blebs failed after approximately 2 weeks based on bleb survival and IOP measurements. No severe complications were observed with OCT and SL. Histology revealed a wide variety of cells, in the bleb and around the microshunt, including polymorphonuclear leucocytes (PMNs), myofibroblasts, and foreign body giant cells, at different PODs. Conclusions Implantation of a poly(styrene- b -isobutylene- b -styrene) microshunt in rabbits resulted in the occurrence of a wide variety of cells during the wound-healing response. Future research should further elucidate the potential of these (earlier often overlooked) cells to target the fibrotic response in vivo—for example, by developing novel antifibrotic drugs, methods for sustained delivery of medications, or augmenting material properties. Translational Relevance Current antifibrotic therapies aim to inhibit myofibroblasts; however, a wide variety of cells are involved in the fibrotic response. Future research focusing on these cells could offer novel methods for reducing the fibrotic response after glaucoma surgery.

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“…Furthermore, in a diseased state, cytokines promote the differentiation of fibroblast to myofibroblast, depositing collagen initially in an attempt to repair cardiac damage [ 29 ]. However, the activation of fibroblasts releases further cytokines to target the ‘wound’, which in turn activates resident macrophages and can perpetuate the immune response [ 30 ]. For example, previous studies have indicated that the activation of macrophages and T cells in hypertensive hearts increases Monocyte Chemoattractant Protein 1 (MCP-1), which maintains immune cell recruitment, leading to sustained inflammation [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Of Mouse and Man: Cross-Species Characterization of Hypertensive Cardiac Remodeling

Cooper

Westaby

Haines

et al. 2022

IJMS

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Hypertension is a major public health concern and poses a significant risk for sudden cardiac death (SCD). However, the characterisation of human tissues tends to be macroscopic, with little appreciation for the quantification of the pathological remodelling responsible for the advancement of the disease. While the components of hypertensive remodelling are well established, the timeline and comparative quantification of pathological changes in hypertension have not been shown before. Here, we sought to identify the phasing of cardiac remodelling with hypertension using post-mortem tissue from SCD patients with early and advanced hypertensive heart disease (HHD). In order to study and quantify the progression of phenotypic changes, human specimens were contrasted to a well-described angiotensin-II-mediated hypertensive mouse model. While cardiomyocyte hypertrophy is an early adaptive response in the mouse that stabilises in established hypertension and declines as the disease progresses, this finding did not translate to the human setting. In contrast, optimising fibrosis quantification methods and applying them to each setting identified perivascular fibrosis as the prevailing possible cause for overall disease progression. Indeed, assessing myocardial inflammation highlights CD45+ inflammatory cell infiltration that precedes fibrosis and is an early-phase event in response to elevated arterial pressures that may underscore perivascular remodelling. Along with aetiology insight, we highlight cross-species comparison for quantification of cardiac remodelling in human hypertension. As such, this platform could assist with the development of therapies specific to the disease phase rather than targeting global components of hypertension, such as blood pressure lowering.

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Is the Macrophage Phenotype Determinant for Fibrosis Development?

Cited by 45 publications

References 188 publications

IFNγ-Treated Macrophages Induce EMT through the WNT Pathway: Relevance in Crohn’s Disease

IFNγ-Treated Macrophages Induce EMT through the WNT Pathway: Relevance in Crohn’s Disease

Wound Healing Response After Bleb-Forming Glaucoma Surgery With a SIBS Microshunt in Rabbits

Of Mouse and Man: Cross-Species Characterization of Hypertensive Cardiac Remodeling

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