Host Responses in Tissue Repair and Fibrosis

By Jeremy S. Duffield, M. Lupher, V. Thannickal, TA Wynn. Annual Review of Pathology, 2012

599 citations recorded by the source corpus.

Myofibroblasts accumulate in the spaces between organ structures and produce extracellular matrix (ECM) proteins, including collagen I. They are the primary “effector” cells in tissue remodeling and fibrosis. Previously, leukocyte progenitors termed fibrocytes and myofibroblasts generated from epithelial cells through epithelial-to-mesenchymal transition (EMT) were considered the primary sources of ECM-producing myofibroblasts in injured tissues. However, genetic fate mapping experiments suggest that mesenchyme-derived cells, known as resident fibroblasts, and pericytes are the primary precursors of scar-forming myofibroblasts, whereas epithelial cells, endothelial cells, and myeloid leukocytes contribute to fibrogenesis predominantly by producing key fibrogenic cytokines and by promoting cell-to-cell communication. Numerous cytokines derived from T cells, macrophages, and other myeloid cell populations are important drivers of myofibroblast differentiation. Monocyte-derived cell populations are key regulators of the fibrotic process: They act as a brake on the processes driving fibrogenesis, and they dismantle and degrade established fibrosis. We discuss the origins, modes of activation, and fate of myofibroblasts in various important fibrotic diseases and describe how manipulation of macrophage activation could help ameliorate fibrosis.

Subfields: Genetics, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/104edf60c75f336011be850c9396141a097ed7e1

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

1. P. Murray
2. S. Friedman
3. Jeremy S. Duffield

In Pulmonary and Respiratory Medicine

1. Jeremy S. Duffield
2. S. Friedman
3. D. Sheppard
4. P. Murray
5. S. Violette
6. V. Thannickal

Citations in the corpus

• Therapy for Fibrotic Diseases: Nearing the Starting Line (2013, background): “The use of fluorescent or enzymatic reporters expressed under the control of lineage-restricted promoters has enabled the identification of large populations of mesenchymal cells in all human organs (126).”
• Reversal of Persistent Fibrosis in Aging by Targeting Nox4-Nrf2 Redox Imbalance (2014, background): “The myofibroblast is a key effector cell in diverse fibrotic disorders (5); this cell type is primarily responsible for extracellular matrix (ECM) synthesis and tissue remodeling in progressive fibrosis (6).”
• Macrophage Polarization. (2017, background): “Similarly, excessive TH2-driven and M2-associated responses are an important part of many fibrotic diseases (36, 72).”
• Cellular and molecular mechanisms in kidney fibrosis. (2014, unknown): “tissue-destructive cells that contribute to nephron dysfunction through release of ROS and inflammatory cytokines (16, 19, 67).”
• Extracellular Matrix Reorganization During Wound Healing and Its Impact on Abnormal Scarring (2015, unknown): “These properties of hypertrophic myofibroblasts may play an important role in hypertrophic scar formation.(119,121,123) In addition, nuclear factor (NF)-jB is upregulated in keloid fibroblasts and its inhibition suppresses cultured keloid fibroblast proliferation and collagen I production,(124,125) ”
• Molecular mechanisms of diabetic kidney disease. (2014, unknown): “Tubule epithelial degeneration, myofibroblast accumulation, and fibrosis play key roles in DKD progression (93).”