Myofibroblast secretome and its auto-/paracrine signaling

Bomb, Ritin; Heckle, Mark; Sun, Yao; Mancarella, Salvatore; Guntaka, Ramareddy V.; Gerling, Ivan; Weber, Karl T.

doi:10.1586/14779072.2016.1147348

Cited by 31 publications

(23 citation statements)

References 100 publications

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“…The critical role of the AngII signaling pathway through fibroblast AT1 receptors in cardiac fibrosis has been well demonstrated [94,[96][97][98]. Likewise, bradykinin receptors, Gi-coupled BR1, and Gq-coupled BR2 have been shown to be expressed in cardiac myofibroblasts [99,100].…”

Section: Signaling Pathways Mediating Ca 2+ Release In Cardiac Fibrobmentioning

confidence: 95%

Ca2+ Signaling in Cardiac Fibroblasts and Fibrosis-Associated Heart Diseases

Feng

Armillei

et al. 2019

JCDD

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Cardiac fibrosis is the excessive deposition of extracellular matrix proteins by cardiac fibroblasts and myofibroblasts, and is a hallmark feature of most heart diseases, including arrhythmia, hypertrophy, and heart failure. This maladaptive process occurs in response to a variety of stimuli, including myocardial injury, inflammation, and mechanical overload. There are multiple signaling pathways and various cell types that influence the fibrogenesis cascade. Fibroblasts and myofibroblasts are central effectors. Although it is clear that Ca2+ signaling plays a vital role in this pathological process, what contributes to Ca2+ signaling in fibroblasts and myofibroblasts is still not wholly understood, chiefly because of the large and diverse number of receptors, transporters, and ion channels that influence intracellular Ca2+ signaling. Intracellular Ca2+ signals are generated by Ca2+ release from intracellular Ca2+ stores and by Ca2+ entry through a multitude of Ca2+-permeable ion channels in the plasma membrane. Over the past decade, the transient receptor potential (TRP) channels have emerged as one of the most important families of ion channels mediating Ca2+ signaling in cardiac fibroblasts. TRP channels are a superfamily of non-voltage-gated, Ca2+-permeable non-selective cation channels. Their ability to respond to various stimulating cues makes TRP channels effective sensors of the many different pathophysiological events that stimulate cardiac fibrogenesis. This review focuses on the mechanisms of Ca2+ signaling in fibroblast differentiation and fibrosis-associated heart diseases and will highlight recent advances in the understanding of the roles that TRP and other Ca2+-permeable channels play in cardiac fibrosis.

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Section: Signaling Pathways Mediating Ca 2+ Release In Cardiac Fibrobmentioning

confidence: 95%

Ca2+ Signaling in Cardiac Fibroblasts and Fibrosis-Associated Heart Diseases

Feng

Armillei

et al. 2019

JCDD

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“…These active myofibroblast cells do not undergo apoptosis after healing and continue to damage the tissues and organs by producing excessive amounts of ECM proteins. The persistent nature of an activated myofibroblast is maintained through molecular feedforward loops by autocrine and paracrine signaling and the influx of inflammatory cells [11, 12]. Reactive oxygen species (ROS) are one such signal that helps maintain the myofibroblast phenotype [13].…”

Section: Introductionmentioning

confidence: 99%

Reactive Oxygen Species Drive Epigenetic Changes in Radiation-Induced Fibrosis

Shrishrimal

Kosmacek

Oberley‐Deegan

2019

Oxidative Medicine and Cellular Longevity

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Radiation-induced fibrosis (RIF) develops months to years after initial radiation exposure. RIF occurs when normal fibroblasts differentiate into myofibroblasts and lay down aberrant amounts of extracellular matrix proteins. One of the main drivers for developing RIF is reactive oxygen species (ROS) generated immediately after radiation exposure. Generation of ROS is known to induce epigenetic changes and cause differentiation of fibroblasts to myofibroblasts. Several antioxidant compounds have been shown to prevent radiation-induced epigenetic changes and the development of RIF. Therefore, reviewing the ROS-linked epigenetic changes in irradiated fibroblast cells is essential to understand the development and prevention of RIF.

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“…The cell proliferation-promoting effect was greater when the cells were co-cultured with multiple 3T3 fibers. Cells secrete various types of cytokines and growth factors into the surrounding microenvironment and the secretome changes the phenotype of other cells via autocrine or paracrine signaling [9][10][11] . The cellular secretome has been used to culture other cells in co-culture system and shown to be effective.…”

Section: Discussionmentioning

confidence: 99%

Cell fibers promote proliferation of co-cultured cells on a dish

Shima

Itou

Takeuchi

2020

Sci Rep

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This paper describes a co-culture method using cell fiber technology. Cell fibers are cell-laden hydrogel microfibers, in which cells are cultured three-dimensionally and allowed to reach more mature state than the conventional two-dimensional cell culture. Cells in the cell fibers are encapsulated by alginate shell. Only cellular secretome is released into the surrounding environment through the shell while the cells were retained by the fiber. With their high handleability and retrievability, we propose to use the cell fibers for co-culture to ensure steady supply of cellular secretome. We cultured mouse C2C12 myoblasts with mouse 3T3 fibroblasts encapsulated in the cell fibers for two days. The number of C2C12 cells increased proportionally to the number of co-cultured 3T3 fibers, suggesting that the secretome of 3T3 fibers promoted survival and proliferation of C2C12 cells. We believe that cell fiber technology is a useful tool for co-culturing cells, and it will contribute to both basic cell biology and tissue engineering with its unique features.Co-culture, in which two or more types of cells are cultured together, is a major method to study interactions between different types of cells in vitro. Cells interact with each other both directly (via physical contact) and indirectly (via secreted molecules; for example, cytokines, growth factors and hormones) and these interactions have an impact on cellular survival, proliferation, differentiation and maturation. To investigate the indirect cellular interactions, two major methods have been established; one using culture inserts and the other using conditioned medium. Culture inserts make upper and lower compartments in culture wells, which enables a concurrent co-culture. Two different types of cells are plated and cultured in the upper and lower compartments. Only cellular secretome, but not the cells themselves, is then transferred between those two compartments through the pores on the bottom of culture inserts, when the pore size is smaller than the cells. On the other hand, in the method that employs conditioned medium, a certain type of cells are cultured and the supernatant containing their secretome (conditioned medium) is collected to subsequently culture the other type of cells. These methods are often employed and have been shown to be effective to study various cellular interactions 1-3 . However, neither of them is highly space-efficient; the number of available cells that provides secretome is limited because of the culture area.Cell fiber is a unique tool for culturing cells three-dimensionally for a long period until they differentiate into a mature tissue 4 . Cell fibers, which are cell-laden hydrogel microfibers formed by using a double-coaxial laminar-flow microfluidic device, consist of two parts; the core containing cells and extra cellular matrix (ECM) proteins such as collagen, and the alginate shell. Various types of cells have been shown to form three-dimensional (3D) tissues in cell fibers; for example, cardiomyocytes, vascular endoth...

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Myofibroblast secretome and its auto-/paracrine signaling

Cited by 31 publications

References 100 publications

Ca2+ Signaling in Cardiac Fibroblasts and Fibrosis-Associated Heart Diseases

Ca2+ Signaling in Cardiac Fibroblasts and Fibrosis-Associated Heart Diseases

Reactive Oxygen Species Drive Epigenetic Changes in Radiation-Induced Fibrosis

Cell fibers promote proliferation of co-cultured cells on a dish

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