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Cited by 1,590

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Evidence that fibroblasts derive from epithelium during tissue fibrosis

Iwano, Masayuki, Plieth, David, Danoff, Theodore M., Xue, Chengsen, Okada, Hirokazu, Neilson, Eric G.·2002·Journal of Clinical Investigation
DOI 10.1172/jci0215518
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Abstract

Interstitial fibroblasts are principal effector cells of organ fibrosis in kidneys, lungs, and liver. While some view fibroblasts in adult tissues as nothing more than primitive mesenchymal cells surviving embryologic development, they differ from mesenchymal cells in their unique expression of fibroblast-specific protein-1 (FSP1). This difference raises questions about their origin. Using bone marrow chimeras and transgenic reporter mice, we show here that interstitial kidney fibroblasts derive from two sources. A small number of FSP1+, CD34– fibroblasts migrate to normal interstitial spaces from bone marrow. More surprisingly, however, FSP1+ fibroblasts also arise in large numbers by local epithelial-mesenchymal transition (EMT) during renal fibrogenesis. Both populations of fibroblasts express collagen type I and expand by cell division during tissue fibrosis. Our findings suggest that a substantial number of organ fibroblasts appear through a novel reversal in the direction of epithelial cell fate. As a general mechanism, this change in fate highlights the potential plasticity of differentiated cells in adult tissues under pathologic conditions.

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Metadata

Authors
Iwano, M., Plieth, D., Danoff, T. M., Xue, C., Okada, H., & Neilson, E. G.
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
2002-08-01
Volume
110
Issue
3
Pages
341-350
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci0215518
OpenAlex
W4244774747
Cited by
1,590
References
2
FWCI
24.04
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: Evidence that fibroblasts derive from epithelium during tissue fibrosis. https://app.cochat.ai/papers/10.1172/jci0215518
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Iwano, M., Plieth, D., Danoff, T. M., Xue, C., Okada, H., & Neilson, E. G. (2002). Evidence that fibroblasts derive from epithelium during tissue fibrosis. Journal of Clinical Investigation. https://doi.org/10.1172/jci0215518

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.