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Origin of fibrosing cells in systemic sclerosis
Sarah Ebmeier1, Valerie Horsley
1aDepartment of Molecular, Cellular and Developmental Biology bDepartment of Dermatology, Yale University, New Haven, Connecticut, USA.
Purpose Of Review:
Systemic sclerosis, an autoimmune disease of unknown origin, is characterized by progressive fibrosis that can affect all organs of the body. To date, there are no effective therapies for the disease. This paucity of treatment options is primarily because of limited understanding of the processes that initiate and promote fibrosis in general and a lack of animal models that specifically emulate the chronic nature of systemic sclerosis. Most models capitulate acute injury-induced fibrosis in specific organs. Yet, regardless of the model a major outstanding question in the field is the cellular origin of fibrosing cells.
Recent Findings:
A multitude of origins have been proposed in a variety of tissues, including resident tissue stroma, fibrocytes, pericytes, adipocytes, epithelial cells and endothelial cells. Developmentally derived fibroblast lineages have recently been elucidated with fibrosing potential in injury models. Increasing data support the pericyte as a fibrosing cell origin in diverse fibrosis models and adipocytes have recently been proposed. Fibrocytes, epithelial cells and endothelial cells also have been examined, although data do not as strongly support these possible origins.
Summary:
In this review, we discuss recent evidence arguing in favor of and against proposed origins of fibrosing cells in diverse models of fibrosis. We highlight outstanding controversies and propose how future research may elucidate how fibrosing cells arise and what processes can be targeted in order to treat systemic sclerosis.
Insights
Systemic sclerosis lacks effective treatments due to unknown fibrotic cell origins. This review examines proposed fibrotic cell sources, highlighting pericytes and adipocytes as potential contributors in fibrosis models.
Area of Science:
- Fibrosis research
- Autoimmune disease mechanisms
- Cell biology
Background:
- Systemic sclerosis is an autoimmune disease causing progressive fibrosis in multiple organs.
- Current treatments for systemic sclerosis are ineffective.
- Understanding fibrosis initiation and promotion is limited, hindering therapy development.
Purpose of the Study:
- To review proposed cellular origins of fibrotic cells in various fibrosis models.
- To discuss evidence supporting and refuting different cell lineages as fibrotic cell sources.
- To identify key controversies and future research directions in fibrosis research.
Main Methods:
- Literature review of recent evidence on fibrotic cell origins.
- Analysis of data from diverse fibrosis models.
- Discussion of proposed cell types including resident stroma, fibrocytes, pericytes, adipocytes, epithelial, and endothelial cells.
Main Results:
- Multiple cell types have been proposed as origins of fibrotic cells.
- Pericytes and adipocytes are increasingly supported as fibrotic cell origins in various models.
- Evidence for fibrocytes, epithelial cells, and endothelial cells is less robust.
Conclusions:
- The cellular origin of fibrotic cells remains a critical question in systemic sclerosis research.
- Further research is needed to elucidate fibrotic cell origins and identify therapeutic targets.
- Targeting fibrotic cell development pathways may offer new treatment strategies for systemic sclerosis.
