Biology of Fibroblasts and Fibrosis

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: 30 September 2024 | Viewed by 3289

Special Issue Editors


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Guest Editor
Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
Interests: fibrosis; scarring; stem cells; biomaterials
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E-Mail Website
Guest Editor
Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
Interests: fibroblasts; fibrosis; tissue reconstruction

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Guest Editor
Department of Surgery, Stanford University, Stanford, CA 94305, USA
Interests: fibrosis; wound healing; skeletal development; stem cell biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Fibroblasts are mesenchymal cells that are not terminally differentiated. Fibroblasts can be activated by a variety of signals that encourage them to synthesize and lay down an extracellular matrix (ECM). As such, fibroblasts are known to play a pivotal role in fibrosis and scarring. Beyond ECM formation, fibroblasts also contribute to fibrosis by regulating proliferation, inflammation, and angiogenesis. The specific signals and molecular pathways that are key to fibroblasts’ fibrotic behavior have not yet been fully elucidated. Targeting these events would hold great promise for a variety of diseases considering the broad role of fibroblasts in organ fibrosis. Fibroblasts have been shown to play a significant role in wide-ranging cases of organ failure, including systemic sclerosis, idiopathic pulmonary fibrosis, liver cirrhosis, kidney fibrosis, and cardiac fibrosis. An exciting area of recent research is the role of fibroblasts in cancer progression and desmoplasia. The existence of numerous fibroblast subtypes has recently been recognized, with fibroblast heterogeneity being dependent on anatomical location, embryological origin, and disease. Myofibroblasts have been shown to display exaggerated ECM production, being sensitive to specific cytokines, chemokines, and growth factors. Understanding the distinct phenotypes of fibroblasts has become of great research interest since the introduction of high-level molecular techniques, including single-cell RNA and ATAC sequencing. As fibroblasts have been shown to play one of the most important roles in establishing fibrosis, understanding their biology is of utmost importance in developing therapies to potentially overcome this disease. We welcome papers that examine the role of fibroblasts in all aspects of their biology:

Topics can include (but are not limited to):

  • Fibroblast heterogeneity;
  • Fibroblast-associated organ fibrosis (liver, lung, skin, heart, and bowel);
  • The role of fibroblasts in stromal cancer interactions;
  • The role of fibroblasts in wound healing and inflammation;
  • Emerging molecular techniques to characterize fibroblasts.

Dr. Michelle Griffin
Prof. Dr. Derrick Wan
Prof. Dr. Michael T. Longaker
Guest Editors

Manuscript Submission Information

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Keywords

  • fibroblasts
  • fibrosis
  • scarring
  • biomarkers
  • cancer-associated fibroblasts
  • regeneration
  • wound healing

Published Papers (2 papers)

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Research

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13 pages, 1894 KiB  
Article
TGF-β Isoforms Affect the Planar and Subepithelial Fibrogenesis of Human Conjunctival Fibroblasts in Different Manners
by Megumi Watanabe, Yuri Tsugeno, Tatsuya Sato, Araya Umetsu, Nami Nishikiori, Masato Furuhashi and Hiroshi Ohguro
Biomedicines 2023, 11(7), 2005; https://doi.org/10.3390/biomedicines11072005 - 15 Jul 2023
Cited by 2 | Viewed by 1030
Abstract
Three highly homologous isoforms of TGF-β, TGF-β-1~3, are involved in the regulation of various pathophysiological conditions such as wound healing processes in different manners, despite the fact that they bind to the same receptors during their activation. The purpose of the current investigation [...] Read more.
Three highly homologous isoforms of TGF-β, TGF-β-1~3, are involved in the regulation of various pathophysiological conditions such as wound healing processes in different manners, despite the fact that they bind to the same receptors during their activation. The purpose of the current investigation was to elucidate the contributions of TGF-β-1 ~3 to the pathology associated with conjunctiva. For this purpose, the biological effects of these TGF-β isoforms on the structural and functional properties of two-dimensional (2D) and three-dimensional (3D) cultured human conjunctival fibroblasts (HconF) were subjected to the following analyses: 1) transendothelial electrical resistance (TEER), a Seahorse cellular metabolic measurement (2D), size and stiffness measurements of the 3D HTM spheroids, and the qPCR gene expression analyses of extracellular matrix (ECM) components (2D and 3D). The TGF-β isoforms caused different effects on the proliferation of the HconF cell monolayer evaluated by TEER measurements. The differences included a significant increase in the presence of 5 ng/mL TGF-β-1 and -2 and a substantial decrease in the presence of 5 ng/mL TGF-β-3, although there were no significant differences in the response to the TGF-β isoforms for cellular metabolism among the three groups. Similar to planar proliferation, the TGF-β isoforms also induced diverse effects toward the mechanical aspects of 3D HconF spheroids, where TGF-β-1 increased stiffness, TGF-β-2 caused no significant effects, and TGF-β-3 caused the downsizing of the spheroids and stiffness enhancement. The mRNA expression of the ECMs were also modulated in diverse manners by the TGF-β isoforms as well as the culture conditions for the 2D vs. 3D isoforms. Many of these TGF-β-3 inducible effects were markedly different from those caused by TGF-β1 and TGF-β-2. The findings presented herein suggest that the three TGF-β isoforms induce diverse and distinctly different effects on cellular properties and the expressions of ECM molecules in HconF and that these changes are independent of cellular metabolism, thereby inducing different effects on the epithelial and subepithelial proliferation of human conjunctiva. Full article
(This article belongs to the Special Issue Biology of Fibroblasts and Fibrosis)
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Review

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16 pages, 2394 KiB  
Review
Understanding Fibroblast Heterogeneity in Form and Function
by Jennifer B. Parker, Caleb Valencia, Deena Akras, Sarah E. DiIorio, Michelle F. Griffin, Michael T. Longaker and Derrick C. Wan
Biomedicines 2023, 11(8), 2264; https://doi.org/10.3390/biomedicines11082264 - 14 Aug 2023
Cited by 2 | Viewed by 1814
Abstract
Historically believed to be a homogeneous cell type that is often overlooked, fibroblasts are more and more understood to be heterogeneous in nature. Though the mechanisms behind how fibroblasts participate in homeostasis and pathology are just beginning to be understood, these cells are [...] Read more.
Historically believed to be a homogeneous cell type that is often overlooked, fibroblasts are more and more understood to be heterogeneous in nature. Though the mechanisms behind how fibroblasts participate in homeostasis and pathology are just beginning to be understood, these cells are believed to be highly dynamic and play key roles in fibrosis and remodeling. Focusing primarily on fibroblasts within the skin and during wound healing, we describe the field’s current understanding of fibroblast heterogeneity in form and function. From differences due to embryonic origins to anatomical variations, we explore the diverse contributions that fibroblasts have in fibrosis and plasticity. Following this, we describe molecular techniques used in the field to provide deeper insights into subpopulations of fibroblasts and their varied roles in complex processes such as wound healing. Limitations to current work are also discussed, with a focus on future directions that investigators are recommended to take in order to gain a deeper understanding of fibroblast biology and to develop potential targets for translational applications in a clinical setting. Full article
(This article belongs to the Special Issue Biology of Fibroblasts and Fibrosis)
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