Monocyte and macrophage derived myofibroblasts: Is it fate? A review of the current evidence

Vierhout, Megan; Ayoub, Anmar; Naiel, Safaa; Yazdanshenas, Parichehr; Revill, Spencer; Reihani, Amir; Dvorkin‐Gheva, Anna; Shi, Wei; Ask, Kjetil

doi:10.1111/wrr.12946

Cited by 47 publications

(32 citation statements)

References 89 publications

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“…[75][76][77][78] Less conventional sources have also been debated, including epithelial and endothelial cells via mesenchymal transition, [79][80][81] circulating fibrocytes or even bona fide macrophages. [82][83][84][85] But it is not only origin that matters for fibroblasts. Different populations of fibroblasts that either have a common progenitor and occupy different locations or have different progenitors that share the same environment; a complexity that is particularly well studied in the dermis of the skin.…”

Section: Fibronectinmentioning

confidence: 99%

A story of fibers and stress: Matrix‐embedded signals for fibroblast activation in the skin

Sawant

Hinz

Schönborn

et al. 2021

Wound Repair Regeneration

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Our skin is continuously exposed to mechanical challenge, including shear, stretch, and compression. The extracellular matrix of the dermis is perfectly suited to resist these challenges and maintain integrity of normal skin even upon large strains. Fibroblasts are the key cells that interpret mechanical and chemical cues in their environment to turnover matrix and maintain homeostasis in the skin of healthy adults. Upon tissue injury, fibroblasts and an exclusive selection of other cells become activated into myofibroblasts with the task to restore skin integrity by forming structurally imperfect but mechanically stable scar tissue. Failure of myofibroblasts to terminate their actions after successful repair or upon chronic inflammation results in dysregulated myofibroblast activities which can lead to hypertrophic scarring and/or skin fibrosis. After providing an overview on the major fibrillar matrix components in normal skin, we will interrogate the various origins of fibroblasts and myofibroblasts in the skin. We then examine the role of the matrix as signaling hub and how fibroblasts respond to mechanical matrix cues to restore order in the confusing environment of a healing wound.

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Section: Fibronectinmentioning

confidence: 99%

A story of fibers and stress: Matrix‐embedded signals for fibroblast activation in the skin

Sawant

Hinz

Schönborn

et al. 2021

Wound Repair Regeneration

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“…Emerging data show that macrophages can differentiate directly into myofibroblast-like cells, which is termed macrophages to myofibroblasts transition ( Tang et al, 2019 ). MMT cells express both myofibroblasts marker (α-SMA) and macrophages marker (CD68 or F4/80), which produce a large amount of ECM proteins ( Vierhout et al, 2021 ). MMT is recognized as an important factor that accelerates fibrotic process ( Liang et al, 2017a ; Feng et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Inhibition of STING/TBK1 Signaling Attenuates Myeloid Fibroblast Activation and Macrophage to Myofibroblast Transition in Renal Fibrosis

Zeng

Gao

et al. 2022

Front. Pharmacol.

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Renal fibrosis is an important pathological biomarker of chronic kidney disease (CKD). Stimulator of interferon genes/TANK binding kinase 1 (STING/TBK1) axis has been identified as the main regulator of innate immune response and closely related to fibrotic disorder. However, the role of STING/TBK1 signaling pathway in kidney fibrosis is still unknown. In this study, we investigated the effect of pharmacological inhibition of STING/TBK1 signaling on renal fibrosis induced by folic acid (FA). In mice, TBK1 was significantly activated in interstitial cells of FA-injured kidneys, which was markedly inhibited by H-151 (a STING inhibitor) treatment. Specifically, pharmacological inhibition of STING impaired bone marrow-derived fibroblasts activation and macrophage to myofibroblast transition in folic acid nephropathy, leading to reduction of extracellular matrix proteins expression, myofibroblasts formation and development of renal fibrosis. Furthermore, pharmacological inhibition of TBK1 by GSK8612 reduced myeloid myofibroblasts accumulation and impeded macrophage to myofibroblast differentiation, resulting in less deposition of extracellular matrix protein and less severe fibrotic lesion in FA-injured kidneys. In cultured mouse bone marrow-derived monocytes, TGF-β1 activated STING/TBK1 signaling. This was abolished by STING or TBK1 inhibitor administration. In addition, GSK8612 treatment decreased levels of α-smooth muscle actin and extracellular matrix proteins and prevents bone marrow-derived macrophages to myofibroblasts transition in vitro. Collectively, our results revealed that STING/TBK1 signaling has a critical role in bone marrow-derived fibroblast activation, macrophages to myofibroblasts transition, and kidney fibrosis progression.

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“…The von Kossa staining pattern suggests that the ecDNA is mineralized, possibly into hydroxyapatite ( 17 , 18 ). The multitude of CD45+/CD68+/α-SMA+ cells in the large calcific type indicates a differentiation of monocytes/macrophages into myofibroblasts ( 19 , 20 ). Both α-SMA- macrophages and α-SMA+ macrophages may contribute to the ecDNA in calcified thrombi.…”

Section: Discussionmentioning

confidence: 99%

Unusual Histopathological Findings in Mechanically Removed Stroke Thrombi – A Multicenter Experience

et al. 2022

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BackgroundSeveral studies have investigated the histopathology of mechanically retrieved thrombi from stroke patients. Thrombi with unusual components constitute about 1–2% of all stroke thrombi in clinical practice. Knowledge about these rare components is limited.ObjectivesTo characterize the histopathology of unusual stroke thrombi from a real-world setting with relation to clinical presentation, patient characteristics and procedural aspects of mechanical thrombectomy.MethodsOne-thousand and eight thrombi retrieved from stroke patients with mechanical thrombectomy at three different hospitals were retrospectively reviewed for unusual histological components. Fifteen thrombi were included in the study for further histopathological analysis. Clinical data and data on procedural aspects were collected.ResultsWe identified six cases with large amounts of extracellular DNA, of which three were calcified. All six cases except one received anticoagulant therapy. We describe two types of calcifications that differ with respect to general calcification morphology, von Kossa staining pattern, macrophage immunophenotype and presence of multinucleated giant cells. Cholesterol-rich (n = 3), adipocyte-like pattern-rich (n = 2), collagen-rich (n = 2) and myxomatous (n = 1) thrombi were also identified and are discussed with regard to pathogenesis and clinical and intervention characteristics. Finally, a thrombus with parts of a vascular wall is described. Suggestions for future studies are made and clinical and technical aspects of the management for these rare but important patients are discussed.ConclusionIn our retrospective multicenter study, we characterized stroke thrombi histopathologically and found subgroups of thrombi defined by presence of rarely seen components. These defined subgroups showed relation to underlying cardiovascular disease, patient characteristics, and mechanical thrombectomy technique. Knowledge about these components may increase our understanding of stroke pathophysiology and influence interventional procedures.

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Monocyte and macrophage derived myofibroblasts: Is it fate? A review of the current evidence

Cited by 47 publications

References 89 publications

A story of fibers and stress: Matrix‐embedded signals for fibroblast activation in the skin

A story of fibers and stress: Matrix‐embedded signals for fibroblast activation in the skin

Pharmacological Inhibition of STING/TBK1 Signaling Attenuates Myeloid Fibroblast Activation and Macrophage to Myofibroblast Transition in Renal Fibrosis

Unusual Histopathological Findings in Mechanically Removed Stroke Thrombi – A Multicenter Experience

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