Matrix stiffness regulates migration of human lung fibroblasts

Shuichi Asano, Satoru Ito, Kota Takahashi, Kishio Furuya, Masashi Kondo, Masahiro Sokabe, Yoshinori Hasegawa

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

In patients with pulmonary diseases such as idiopathic pulmonary fibrosis and severe acute respiratory distress syndrome, progressive pulmonary fibrosis is caused by dysregulated wound healing via activation of fibroblasts after lung inflammation or severe damage. Migration of fibroblasts toward the fibrotic lesions plays an important role in pulmonary fibrosis. Fibrotic tissue in the lung is much stiffer than normal lung tissue. Emerging evidence supports the hypothesis that the stiffness of the matrix is not only a consequence of fibrosis, but also can induce fibroblast activation. Nevertheless, the effects of substrate rigidity on migration of lung fibroblasts have not been fully elucidated. We evaluated the effects of substrate stiffness on the morphology, α-smooth muscle actin (α-SMA) expression, and cell migration of primary human lung fibroblasts by using polyacrylamide hydrogels with stiffnesses ranging from 1 to 50 kPa. Cell motility was assessed by platelet-derived growth factor (PDGF)-induced chemotaxis and random walk migration assays. As the stiffness of substrates increased, fibroblasts became spindle-shaped and spread. Expression of α-SMA proteins was higher on the stiffer substrates (25 kPa gel and plastic dishes) than on the soft 2 kPa gel. Both PDGF-induced chemotaxis and random walk migration of fibroblasts precultured on stiff substrates (25 kPa gel and plastic dishes) were significantly higher than those of cells precultured on 2 kPa gel. Transfection of the fibroblasts with short interfering RNA for α-SMA inhibited cell migration. These findings suggest that fibroblast activation induced by a stiff matrix is involved in mechanisms of the pathophysiology of pulmonary fibrosis.

Original languageEnglish
Article numbere13281
JournalPhysiological Reports
Volume5
Issue number9
DOIs
Publication statusPublished - 01-05-2017

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Fibroblasts
Lung
Pulmonary Fibrosis
Gels
Cell Movement
Platelet-Derived Growth Factor
Chemotaxis
Plastics
Severe Acute Respiratory Syndrome
Idiopathic Pulmonary Fibrosis
Adult Respiratory Distress Syndrome
Wound Healing
Small Interfering RNA
Lung Diseases
Smooth Muscle Myocytes
Transfection
Actins
Pneumonia
Fibrosis
Proteins

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

Cite this

Asano, S., Ito, S., Takahashi, K., Furuya, K., Kondo, M., Sokabe, M., & Hasegawa, Y. (2017). Matrix stiffness regulates migration of human lung fibroblasts. Physiological Reports, 5(9), [e13281]. https://doi.org/10.14814/phy2.13281
Asano, Shuichi ; Ito, Satoru ; Takahashi, Kota ; Furuya, Kishio ; Kondo, Masashi ; Sokabe, Masahiro ; Hasegawa, Yoshinori. / Matrix stiffness regulates migration of human lung fibroblasts. In: Physiological Reports. 2017 ; Vol. 5, No. 9.
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Asano, S, Ito, S, Takahashi, K, Furuya, K, Kondo, M, Sokabe, M & Hasegawa, Y 2017, 'Matrix stiffness regulates migration of human lung fibroblasts', Physiological Reports, vol. 5, no. 9, e13281. https://doi.org/10.14814/phy2.13281

Matrix stiffness regulates migration of human lung fibroblasts. / Asano, Shuichi; Ito, Satoru; Takahashi, Kota; Furuya, Kishio; Kondo, Masashi; Sokabe, Masahiro; Hasegawa, Yoshinori.

In: Physiological Reports, Vol. 5, No. 9, e13281, 01.05.2017.

Research output: Contribution to journalArticle

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AU - Asano, Shuichi

AU - Ito, Satoru

AU - Takahashi, Kota

AU - Furuya, Kishio

AU - Kondo, Masashi

AU - Sokabe, Masahiro

AU - Hasegawa, Yoshinori

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