Sonic Hedgehog Promotes Proliferation and Migration of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via Rho/ROCK Signaling

Objective. To explore the underlying mechanism of the sonic hedgehog (Shh) signaling pathway in promoting cell proliferation and migration in fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). Method. FLS were collected from 8 patients with RA and 3 patients with osteoa...

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Main Authors: Zaiying Hu, Yingdi Chen, Shangling Zhu, Xiaoxue Feng, Baiyu Zhang, Jianlin Huang
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2022/3423692
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author Zaiying Hu
Yingdi Chen
Shangling Zhu
Xiaoxue Feng
Baiyu Zhang
Jianlin Huang
author_facet Zaiying Hu
Yingdi Chen
Shangling Zhu
Xiaoxue Feng
Baiyu Zhang
Jianlin Huang
author_sort Zaiying Hu
collection DOAJ
description Objective. To explore the underlying mechanism of the sonic hedgehog (Shh) signaling pathway in promoting cell proliferation and migration in fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). Method. FLS were collected from 8 patients with RA and 3 patients with osteoarthritis (OA). The expression of smoothened (Smo, the Shh pathway activator) was quantified by real-time PCR and western blot. FLS were incubated with cyclopamine (a Smo antagonist), purmorphamine (a Smo agonist), Y27632 (a Rho/ROCK signaling inhibitor), or a combination of purmorphamine and Y27632, respectively. Cell proliferation was examined using cell counting kit-8 and cell cycle assays while cell migration was measured with Transwell and wound healing assays. Results. The expression of Smo was higher in FLS from RA patients than from OA patients (p<0.05). RA-FLS treated with purmorphamine showed significantly activated proliferation (119.69 vs. 100.0) and migration (252.38 vs. 178.57) compared to untreated cells (both p<0.001). RA-FLS incubated with cyclopamine or a combination of purmorphamine and Y27632 exhibited significant suppression of proliferation (81.55 vs. 100.0 and 85.84 vs. 100.0) and migration (100 vs. 178.57 and 109.52 vs. 185) ability (all p<0.001). Conclusion. Our results demonstrated that Shh promoted cell growth and migration of FLS in RA patients through the Rho/ROCK signaling pathway.
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spelling doaj-art-50f377aa22b44e9ea619afced5216eb22025-08-20T03:18:09ZengWileyJournal of Immunology Research2314-71562022-01-01202210.1155/2022/3423692Sonic Hedgehog Promotes Proliferation and Migration of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via Rho/ROCK SignalingZaiying Hu0Yingdi Chen1Shangling Zhu2Xiaoxue Feng3Baiyu Zhang4Jianlin Huang5Department of RheumatologyDepartment of RheumatologyDepartment of RheumatologyDepartment of RheumatologyDepartment of RheumatologyDepartment of RheumatologyObjective. To explore the underlying mechanism of the sonic hedgehog (Shh) signaling pathway in promoting cell proliferation and migration in fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). Method. FLS were collected from 8 patients with RA and 3 patients with osteoarthritis (OA). The expression of smoothened (Smo, the Shh pathway activator) was quantified by real-time PCR and western blot. FLS were incubated with cyclopamine (a Smo antagonist), purmorphamine (a Smo agonist), Y27632 (a Rho/ROCK signaling inhibitor), or a combination of purmorphamine and Y27632, respectively. Cell proliferation was examined using cell counting kit-8 and cell cycle assays while cell migration was measured with Transwell and wound healing assays. Results. The expression of Smo was higher in FLS from RA patients than from OA patients (p<0.05). RA-FLS treated with purmorphamine showed significantly activated proliferation (119.69 vs. 100.0) and migration (252.38 vs. 178.57) compared to untreated cells (both p<0.001). RA-FLS incubated with cyclopamine or a combination of purmorphamine and Y27632 exhibited significant suppression of proliferation (81.55 vs. 100.0 and 85.84 vs. 100.0) and migration (100 vs. 178.57 and 109.52 vs. 185) ability (all p<0.001). Conclusion. Our results demonstrated that Shh promoted cell growth and migration of FLS in RA patients through the Rho/ROCK signaling pathway.http://dx.doi.org/10.1155/2022/3423692
spellingShingle Zaiying Hu
Yingdi Chen
Shangling Zhu
Xiaoxue Feng
Baiyu Zhang
Jianlin Huang
Sonic Hedgehog Promotes Proliferation and Migration of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via Rho/ROCK Signaling
Journal of Immunology Research
title Sonic Hedgehog Promotes Proliferation and Migration of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via Rho/ROCK Signaling
title_full Sonic Hedgehog Promotes Proliferation and Migration of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via Rho/ROCK Signaling
title_fullStr Sonic Hedgehog Promotes Proliferation and Migration of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via Rho/ROCK Signaling
title_full_unstemmed Sonic Hedgehog Promotes Proliferation and Migration of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via Rho/ROCK Signaling
title_short Sonic Hedgehog Promotes Proliferation and Migration of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via Rho/ROCK Signaling
title_sort sonic hedgehog promotes proliferation and migration of fibroblast like synoviocytes in rheumatoid arthritis via rho rock signaling
url http://dx.doi.org/10.1155/2022/3423692
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