Smoothened regulates migration of fibroblast-like synoviocytes in rheumatoid arthritis Via activation of rho GTPase signaling

Wei Xiang Peng, Shang Ling Zhu, Bai Yu Zhang, Yi Ming Shi, Xiao Xue Feng, Fang Liu, Jian Lin Huang, Song Guo Zheng

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Fibroblast-like synoviocytes (FLSs) acquire aggressive phenotypes characterized with enhanced migration abilities and inherent invasive qualities in rheumatoid arthritis (RA). Smoothened (Smo) is a key component of sonic hedgehog (Shh) signaling and contributes to tumor cell invasion and metastasis. The objective of this study is to investigate the role of Smo in the modulation of cell migration and explore the underlying molecular mechanism(s). FLSs were isolated from RA synovium. Shh levels were regulated by a Smo agonist (purmorphamine), Smo antagonist (KAAD-cyclopamine), or small interfering RNA targeting the Smo gene (Smo-siRNA) in RA-FLSs. Expression of Smo was detected by real-time PCR and western blot analysis. Cell migration was examined by Transwell assay and activation of Rho GTPases was measured by pull-down assays. Incubation with purmorphamine resulted in a significant increase of cell migration and activation of Rho GTPase signaling compared to controls (P < 0.05). However, treatment with KAAD-cyclopamine or transfection with Smo-siRNA suppressed migration of RA-FLSs and showed an inhibitory effect of Rho GTPase signaling. Together, these results suggest that Smo plays an important role in RA-FLSs migration through activation of Rho GTPase signaling and may contribute to progression of RA, thus, targeting Shh signal may have a therapeutic potential in patients with RA.

Original languageEnglish (US)
Article number159
JournalFrontiers in immunology
Volume8
Issue numberFEB
DOIs
StatePublished - Feb 15 2017

Fingerprint

rho GTP-Binding Proteins
Rheumatoid Arthritis
Fibroblasts
Small Interfering RNA
Cell Movement
Gene Targeting
Synovial Membrane
Synoviocytes
Transfection
Real-Time Polymerase Chain Reaction
Western Blotting
Neoplasm Metastasis
Phenotype
Therapeutics

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Peng, Wei Xiang ; Zhu, Shang Ling ; Zhang, Bai Yu ; Shi, Yi Ming ; Feng, Xiao Xue ; Liu, Fang ; Huang, Jian Lin ; Zheng, Song Guo. / Smoothened regulates migration of fibroblast-like synoviocytes in rheumatoid arthritis Via activation of rho GTPase signaling. In: Frontiers in immunology. 2017 ; Vol. 8, No. FEB.
@article{eb895a6870af44f4854d9ef86e631aed,
title = "Smoothened regulates migration of fibroblast-like synoviocytes in rheumatoid arthritis Via activation of rho GTPase signaling",
abstract = "Fibroblast-like synoviocytes (FLSs) acquire aggressive phenotypes characterized with enhanced migration abilities and inherent invasive qualities in rheumatoid arthritis (RA). Smoothened (Smo) is a key component of sonic hedgehog (Shh) signaling and contributes to tumor cell invasion and metastasis. The objective of this study is to investigate the role of Smo in the modulation of cell migration and explore the underlying molecular mechanism(s). FLSs were isolated from RA synovium. Shh levels were regulated by a Smo agonist (purmorphamine), Smo antagonist (KAAD-cyclopamine), or small interfering RNA targeting the Smo gene (Smo-siRNA) in RA-FLSs. Expression of Smo was detected by real-time PCR and western blot analysis. Cell migration was examined by Transwell assay and activation of Rho GTPases was measured by pull-down assays. Incubation with purmorphamine resulted in a significant increase of cell migration and activation of Rho GTPase signaling compared to controls (P < 0.05). However, treatment with KAAD-cyclopamine or transfection with Smo-siRNA suppressed migration of RA-FLSs and showed an inhibitory effect of Rho GTPase signaling. Together, these results suggest that Smo plays an important role in RA-FLSs migration through activation of Rho GTPase signaling and may contribute to progression of RA, thus, targeting Shh signal may have a therapeutic potential in patients with RA.",
author = "Peng, {Wei Xiang} and Zhu, {Shang Ling} and Zhang, {Bai Yu} and Shi, {Yi Ming} and Feng, {Xiao Xue} and Fang Liu and Huang, {Jian Lin} and Zheng, {Song Guo}",
year = "2017",
month = "2",
day = "15",
doi = "10.3389/fimmu.2017.00159",
language = "English (US)",
volume = "8",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media S. A.",
number = "FEB",

}

Smoothened regulates migration of fibroblast-like synoviocytes in rheumatoid arthritis Via activation of rho GTPase signaling. / Peng, Wei Xiang; Zhu, Shang Ling; Zhang, Bai Yu; Shi, Yi Ming; Feng, Xiao Xue; Liu, Fang; Huang, Jian Lin; Zheng, Song Guo.

In: Frontiers in immunology, Vol. 8, No. FEB, 159, 15.02.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Smoothened regulates migration of fibroblast-like synoviocytes in rheumatoid arthritis Via activation of rho GTPase signaling

AU - Peng, Wei Xiang

AU - Zhu, Shang Ling

AU - Zhang, Bai Yu

AU - Shi, Yi Ming

AU - Feng, Xiao Xue

AU - Liu, Fang

AU - Huang, Jian Lin

AU - Zheng, Song Guo

PY - 2017/2/15

Y1 - 2017/2/15

N2 - Fibroblast-like synoviocytes (FLSs) acquire aggressive phenotypes characterized with enhanced migration abilities and inherent invasive qualities in rheumatoid arthritis (RA). Smoothened (Smo) is a key component of sonic hedgehog (Shh) signaling and contributes to tumor cell invasion and metastasis. The objective of this study is to investigate the role of Smo in the modulation of cell migration and explore the underlying molecular mechanism(s). FLSs were isolated from RA synovium. Shh levels were regulated by a Smo agonist (purmorphamine), Smo antagonist (KAAD-cyclopamine), or small interfering RNA targeting the Smo gene (Smo-siRNA) in RA-FLSs. Expression of Smo was detected by real-time PCR and western blot analysis. Cell migration was examined by Transwell assay and activation of Rho GTPases was measured by pull-down assays. Incubation with purmorphamine resulted in a significant increase of cell migration and activation of Rho GTPase signaling compared to controls (P < 0.05). However, treatment with KAAD-cyclopamine or transfection with Smo-siRNA suppressed migration of RA-FLSs and showed an inhibitory effect of Rho GTPase signaling. Together, these results suggest that Smo plays an important role in RA-FLSs migration through activation of Rho GTPase signaling and may contribute to progression of RA, thus, targeting Shh signal may have a therapeutic potential in patients with RA.

AB - Fibroblast-like synoviocytes (FLSs) acquire aggressive phenotypes characterized with enhanced migration abilities and inherent invasive qualities in rheumatoid arthritis (RA). Smoothened (Smo) is a key component of sonic hedgehog (Shh) signaling and contributes to tumor cell invasion and metastasis. The objective of this study is to investigate the role of Smo in the modulation of cell migration and explore the underlying molecular mechanism(s). FLSs were isolated from RA synovium. Shh levels were regulated by a Smo agonist (purmorphamine), Smo antagonist (KAAD-cyclopamine), or small interfering RNA targeting the Smo gene (Smo-siRNA) in RA-FLSs. Expression of Smo was detected by real-time PCR and western blot analysis. Cell migration was examined by Transwell assay and activation of Rho GTPases was measured by pull-down assays. Incubation with purmorphamine resulted in a significant increase of cell migration and activation of Rho GTPase signaling compared to controls (P < 0.05). However, treatment with KAAD-cyclopamine or transfection with Smo-siRNA suppressed migration of RA-FLSs and showed an inhibitory effect of Rho GTPase signaling. Together, these results suggest that Smo plays an important role in RA-FLSs migration through activation of Rho GTPase signaling and may contribute to progression of RA, thus, targeting Shh signal may have a therapeutic potential in patients with RA.

UR - http://www.scopus.com/inward/record.url?scp=85014404220&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85014404220&partnerID=8YFLogxK

U2 - 10.3389/fimmu.2017.00159

DO - 10.3389/fimmu.2017.00159

M3 - Article

C2 - 28261216

AN - SCOPUS:85014404220

VL - 8

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

IS - FEB

M1 - 159

ER -