Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 360

The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.

Interstitial fluid flow induces myofibroblast differentiation and collagen alignment in vitro

Open access
Ng, Chee Ping, Hinz, Boris, Swartz, Melody A.·2005·Journal of Cell Science
DOI 10.1242/jcs.02605
Open this paper in CoChat — free account

Abstract

The differentiation of fibroblasts to contractile myofibroblasts, which is characterized by de novo expression of α-smooth muscle actin (α-SMA), is crucial for wound healing and a hallmark of tissue scarring and fibrosis. These processes often follow inflammatory events, particularly in soft tissues such as skin, lung and liver. Although inflammatory cells and damaged epithelium can release transforming growth factor β1 (TGF-β1), which largely mediates myofibroblast differentiation, the biophysical environment of inflammation and tissue regeneration, namely increased interstitial flow owing to vessel hyperpermeability and/or angiogenesis, may also play a role. We demonstrate that low levels of interstitial (3D) flow induce fibroblast-to-myofibroblast differentiation as well as collagen alignment and fibroblast proliferation, all in the absence of exogenous mediators. These effects were associated with TGF-β1 induction, and could be eliminated with TGF-β1 blocking antibodies. Furthermore, α1β1 integrin was seen to play an important role in the specific response to flow, as its inhibition prevented fibroblast differentiation and subsequent collagen alignment but did not block their ability to contract the gel in a separate floating gel assay. This study suggests that the biophysical environment that often precedes fibrosis, such as swelling, increased microvascular permeability and increased lymphatic drainage – all which involve interstitial fluid flow – may itself play an important role in fibrogenesis.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1242/jcs.02605

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 4 references

Research works printed but not linked: 55

  1. Arora, P. D. and McCulloch, C. A. G. (1994). Dependence of collagen remodeling on alpha-smooth muscle actin expression by fibroblasts. J. Cell. Physiol.159, 161-175. · DOI · Paper page
  2. Arora, P. D., Narani, N. and McCulloch, C. A. G. (1999). The compliance of collagen gels regulates transforming growth factor-beta induction of alpha-smooth muscle actin in fibroblasts. Am. J. Pathol.154, 871-882. · DOI · Paper page
  3. Barakat, A. and Lieu, D. (2003). Differential responsiveness of vascular endothelial cells to different types of fluid mechanical shear stress. Cell Biochem. Biophys.38, 323-343. · DOI
  4. Brightman, A. O., Rajwa, B. P., Sturgis, J. E., McCallister, M. E., Robinson, J. P. and Voytik-Harbin, S. L. (2000). Time-lapse confocal reflection microscopy of collagen fibrillogenesis and extracellular matrix assembly in vitro. Biopolymers54, 222-234. · DOI · Paper page
  5. Campisi, C. and Boccardo, F. (2002). Lymphedema and microsurgery. Microsurgery22, 74-80. · doi:10.1002/micr.21728
  6. Chary, S. R. and Jain, R. K. (1989). Direct measurement of interstitial convection and diffusion of albumin in normal and neoplastic tissues by fluorescence photobleaching. Proc. Natl. Acad. Sci. USA86, 5385-5389. · DOI · Paper page
  7. Chaudhuri, S., Nguyen, H., Rangayyan, R. M., Walsh, S. and Frank, C. B. (1987). A Fourier domain directional filtering method for analysis of collagen alignment in ligaments. IEEE Trans. Biomed. Eng.34, 509-518. · DOI
  8. Danen, E. H. J. and Sonnenberg, A. (2003). Integrins in regulation of tissue development and function. J. Pathol.201, 632-641. · DOI · Paper page
  9. Desmouliere, A., Geinoz, A., Gabbiani, F. and Gabbiani, G. (1993). Transforming growth factor beta-1 induces alpha-smooth muscle actin expression in granulation-tissue myofibroblasts and in quiescent and growing cultured fibroblasts. J. Cell Biol.122, 103-111. · DOI · Paper page
  10. Desmouliere, A., Darby, I. A. and Gabbiani, G. (2003). Normal and pathologic soft tissue remodeling: Role of the myofibroblast, with special emphasis on liver and kidney fibrosis. Lab. Invest.83, 1689-1707. · DOI · Paper page
  11. Desmouliere, A., Guyot, C. and Gabbiani, C. (2004). The stroma reaction myofibroblast: a key player in the control of tumor cell behavior. Int. J. Dev. Biol.48, 509-517. · DOI · Paper page
  12. Dugina, V., Fontao, L., Chaponnier, C., Vasiliev, J. and Gabbiani, G. (2001). Focal adhesion features during myofibroblastic differentiation are controlled by intracellular and extracellular factors. J. Cell Sci.114, 3285-3296. · DOI · Paper page
  13. Eckes, B., Kessler, D., Aumailley, M. and Krieg, T. (1999). Interactions of fibroblasts with the extracellular matrix: implications for the understanding of fibrosis. Sem. Immunopathol.21, 415-429. · DOI
  14. Ehrlich, H. P. and Krummel, T. M. (1996). Regulation of wound healing from a connective tissue perspective. Wound Repair Regen.4, 203-210. · DOI
  15. Gabbiani, G. (2003). The myofibroblast in wound healing and fibrocontractive diseases. J. Pathol.200, 500-503. · DOI · Paper page
  16. Grinnell, F. (1994). Fibroblasts, myofibroblasts, and wound contraction. J. Cell Biol.124, 401-404. · DOI · Paper page
  17. Grinnell, F., Ho, C. H., Tamariz, E., Lee, D. J. and Skuta, G. (2003). Dendritic fibroblasts in three-dimensional collagen matrices. Mol. Biol. Cell14, 384-395. · DOI · Paper page
  18. Heino, J. (2000). The collagen receptor integrins have distinct ligand recognition and signaling functions. Matrix Biol.19, 319-323. · DOI · Paper page
  19. Hinz, B., Celetta, G., Tomasek, J. J., Gabbiani, G. and Chaponnier, C. (2001a). Alpha-smooth muscle actin expression upregulates fibroblast contractile activity. Mol. Biol. Cell12, 2730-2741. · DOI · Paper page
  20. Hinz, B., Mastrangelo, D., Iselin, C. E., Chaponnier, C. and Gabbiani, G. (2001b). Mechanical tension controls granulation tissue contractile activity and myofibroblast differentiation. Am. J. Pathol.159, 1009-1020. · DOI · Paper page
  21. Hinz, B. and Gabbiani, C. (2003a). Mechanisms of force generation and transmission by myofibroblasts. Curr. Opin. Biotechnol.14, 538-546. · DOI · Paper page
  22. Hinz, B. and Gabbiani, G. (2003b). Cell-matrix and cell-cell contacts of myofibroblasts: role in connective tissue remodeling. Thromb. Haemost.90, 993-1002. · DOI · Paper page
  23. Jain, R. K. (2001). Delivery of molecular and cellular medicine to solid tumors. Adv. Drug Deliv. Rev.46, 149-168. · DOI · Paper page
  24. Jenkins, G., Redwood, K. L., Meadows, L. and Green, M. R. (1999). Effect of gel reorganization and tensional forces on alpha 2 beta 1 integrin levels in dermal fibroblasts. Eur. J. Biochem.263, 93-103. · doi:10.1046/j.1432-1327.1999.00468.x
  25. Kim, S. J., Angel, P., Lafyatis, R., Hattori, K., Kim, K. Y., Sporn, M. B., Karin, M. and Roberts, A. B. (1990). Autoinduction of transforming growth factor-beta-1 is mediated by the Ap-1 complex. Mol. Cell. Biol.10, 1492-1497. · DOI · Paper page
  26. Langholz, O., Rockel, D., Mauch, C., Kozlowska, E., Bank, I., Krieg, T. and Eckes, B. (1995). Collagen and collagenase gene expression in three-dimensional collagen lattices are differentially regulated by alpha 1 beta 1 and alpha 2 beta 1 integrins. J. Cell Biol.131, 1903-1915. · DOI · Paper page
  27. Lee, A. A., Graham, D. A., Dela Cruz, S., Ratcliffe, A. and Karlon, W. J. (2002). Fluid shear stress-induced alignment of cultured vascular smooth muscle cells. J. Biomech. Eng.124, 37-43. · DOI
  28. Li, S. H., Van den Diepstraten, C., D'Souza, S. J., Chan, B. M. C. and Pickering, J. G. (2003). Vascular smooth muscle cells orchestrate the assembly of type I collagen via alpha 2 beta 1 integrin, RhoA, and fibronectin polymerization. Am. J. Pathol.163, 1045-1056. · DOI · Paper page
  29. Martin, P. (1997). Wound healing – aiming for perfect skin regeneration. Science276, 75-81. · DOI · Paper page
  30. Mueller, M. M. and Fusenig, N. E. (2004). Friends or foes – bipolar effects of the tumour stroma in cancer. Nat. Rev. Cancer4, 839-849. · DOI · Paper page
  31. Mutsaers, S. E., Bishop, J. E., McGrouther, G. and Laurent, G. J. (1997). Mechanisms of tissue repair: from wound healing to fibrosis. Int. J. Biochem. Cell Biol.29, 5-17. · DOI · Paper page
  32. Ng, C. P. and Swartz, M. A. (2003). Fibroblast alignment under interstitial fluid flow using a novel 3-D tissue culture model. Am. J. Physiol.284, H1771-H1777. · DOI · Paper page
  33. Ng, C. P., Helm, C. E. and Swartz, M. A. (2004). Interstitial flow differentially stimulates blood and lymphatic endothelial cell morphogenesis in vitro. Microvasc. Res.68, 258-264. · DOI · Paper page
  34. Nishimura, T. and Ansell, M. P. (2002). Fast Fourier transform and filtered image analyses of fiber orientation in OSB. Wood Sci. Technol.36, 287-307. · doi:10.1007/s002260100114
  35. Phan, S. H. (2002). The myofibroblast in pulmonary fibrosis. Chest122, 286S-289S. · DOI · Paper page
  36. Pourdeyhimi, B., Dent, R. and Davis, H. (1997). Measuring fiber orientation in nonwovens: 3. Fourier transform. Textile Res. J.67, 143-151. · doi:10.1177/004051759706700211
  37. Racine-Samson, L., Rockey, D. C. and Bissell, D. M. (1997). The role of alpha 1 beta 1 integrin in wound contraction: a quantitative analysis of liver myofibroblasts in vivo and in primary culture. J. Biol. Chem.272, 30911-30917. · DOI · Paper page
  38. Rettig, W. J., Dracopoli, N. C., Goetzger, T. A., Spengler, B. A., Biedler, J. L., Oettgen, H. F. and Old, L. J. (1984). Somatic cell genetic analysis of human cell surface antigens – chromosomal assignments and regulation of expression in rodent human hybrid cells. Proc. Natl. Acad. Sci. USA81, 6437-6441. · DOI
  39. Roberts, A. B., Sporn, M. B., Assoian, R. K., Smith, J. M., Roche, N. S., Wakefield, L. M., Heine, U. I., Liotta, L. A., Falanga, V., Kehrl, J. H. et al. (1986). Transforming growth factor type beta – rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc. Natl. Acad. Sci. USA83, 4167-4171. · DOI · Paper page
  40. Schiro, J. A., Chan, B. M., Roswit, W. T., Kassner, P. D., Pentland, A. P., Hemler, M. E., Eisen, A. Z. and Kupper, T. S. (1991). Integrin alpha 2 beta 1 (VLA-2) mediates reorganization and contraction of collagen matrices by human cells. Cell67, 403-410. · DOI · Paper page
  41. Serini, G. and Gabbiani, G. (1999). Mechanisms of myofibroblast activity and phenotypic modulation. Exp. Cell Res.250, 273-283. · DOI · Paper page
  42. Setty, S., Kim, Y., Fields, G. B., Clegg, D. O., Wayner, E. A. and Tsilibary, E. C. (1998). Interactions of type IV collagen and its domains with human mesangial cells. J. Biol. Chem.273, 12244-12249. · DOI
  43. Song, R. H., Kocharyan, H. K., Fortunato, J. E., Glagov, S. and Bassiouny, H. S. (2000). Increased flow and shear stress enhance in vivo transforming growth factor-beta 1 after experimental arterial injury. Arterioscler. Thromb. Vasc. Biol.20, 923-930. · DOI
  44. Swartz, M. A. (2003). Signaling in morphogenesis: transport cues in morphogenesis. Curr. Opin. Biotech.14, 547-550. · DOI
  45. Tamariz, E. and Grinnell, F. (2002). Modulation of fibroblast morphology and adhesion during collagen matrix remodeling. Mol. Biol. Cell13, 3915-3929 · DOI · Paper page
  46. Thannickal, V. J., Toews, G. B., White, E. S., Lynch, J. P. and Martinez, F. J. (2004). Mechanisms of pulmonary fibrosis. Ann. Rev. Med.55, 395-417. · DOI · Paper page
  47. Ueba, H., Kawakami, M. and Yaginuma, T. (1997). Shear stress as an inhibitor of vascular smooth muscle cell proliferation – Role of transforming growth factor-beta 1 and tissue-type plasminogen activator. Arterioscler. Thromb. Vasc. Biol.17, 1512-1516. · DOI
  48. van Zuijlen, P. P. M., de Vries, H. J. C., Lamme, E. N., Coppens, J. S. E., van Marle, J., Kreis, R. W. and Middelkoop, E. (2002). Morphometry of dermal collagen orientation by Fourier analysis is superior to multi-observer assessment. J. Pathol.198, 284-291. · DOI
  49. Vanni, S., Lagerholm, B. C., Otey, C., Taylor, D. L. and Lanni, F. (2003). Internet-based image analysis quantifies contractile behavior of individual fibroblasts inside model tissue. Biophys. J.84, 2715-2727. · DOI
  50. Varga, J. and Jimenez, S. A. (1995). Modulation of collagen gene expression – its relation to fibrosis in systemic sclerosis and other disorders. Ann. Int. Med.122, 60-62. · DOI
  51. Vaughan, M. B., Howard, E. W. and Tomasek, J. J. (2000). Transforming growth factor-beta1 promotes the morphological and functional differentiation of the myofibroblast. Exp. Cell Res.257, 180-189. · DOI · Paper page
  52. Walker, R. A. (2001). The complexities of breast cancer desmoplasia. Breast Cancer Res.3, 143-145. · DOI · Paper page
  53. Wang, D. M. and Tarbell, J. M. (1995). Modeling interstitial flow in an artery wall allows estimation of wall shear stress on smooth muscle cells. J. Biomech. Eng.117, 358-363. · DOI · Paper page
  54. Werner, S. and Grose, R. (2003). Regulation of wound healing by growth factors and cytokines. Physiol. Rev.83, 835-870. · DOI · Paper page
  55. Zhang, H. Y. and Phan, S. H. (1999). Inhibition of myofibroblast apoptosis by transforming growth factor beta(1). Am. J. Resp. Cell Mol. Biol.21, 658-665. · DOI · Paper page

Cited by

See all 360

Metadata

Authors
Ng, C. P., Hinz, B., & Swartz, M. A.
Venue
Journal of Cell Science
Publisher
The Company of Biologists
Published
2005-10-15
Volume
118
Issue
20
Pages
4731-4739
ISSN
  • 0021-9533 (ISSN-L)
  • 1477-9137
DOI
10.1242/jcs.02605
OpenAlex
W2112497501
Cited by
360
References
4
FWCI
8.72
Type
journal article
Language
en
Open access
green

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Interstitial fluid flow induces myofibroblast differentiation and collagen alignment in vitro. https://app.cochat.ai/papers/10.1242/jcs.02605
The paper
Ng, C. P., Hinz, B., & Swartz, M. A. (2005). Interstitial fluid flow induces myofibroblast differentiation and collagen alignment in vitro. Journal of Cell Science. https://doi.org/10.1242/jcs.02605

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

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.