The CLC-2 Chloride Channel Modulates ECM Synthesis, Differentiation, and Migration of Human Conjunctival Fibroblasts via the PI3K/Akt Signaling Pathway.
Recent evidence suggests that chloride channels are critical for cell proliferation, migration, and differentiation. We examined the effects of transforming growth factor (TGF)-β1 on chloride channel expression and associations with human conjunctival fibroblast (HConF) biology. To investigate the potential role of chloride channel (CLC)-2 in migration, transition to myofibroblasts and extracellular matrix (ECM) synthesis of HconF, a small interfering RNA (siRNA) approach was applied. TGF-β1-induced migration and transition of fibroblasts to myofibroblasts characterized by α-smooth muscle actin (α-SMA) expression, supported by increased endogenous expression of CLC-2 protein and mRNA transcripts. ECM (collagen I and fibronectin) synthesis in HConF was enhanced by TGF-β1. CLC-2 siRNA treatment reduced TGF-β1-induced cell migration, transition of fibroblasts to myofibroblasts, and ECM synthesis of HConF. CLC-2 siRNA treatment in the presence of TGF-β1 inhibited phosphorylation of PI3K and Akt in HConF. These findings demonstrate that CLC-2 chloride channels are important for TGF-β1-induced migration, differentiation, and ECM synthesis via PI3K/Akt signaling in HConF.
Department of Ophthalmology, Second Hospital of Jilin University, Jilin University, Changchun 130041, China. sunlx_2008@163.com.
Lixia
L
Sun
Department of Ophthalmology, Second Hospital of Jilin University, Jilin University, Changchun 130041, China. dongyaru@sina.com.
Yaru
Y
Dong
Department of Ophthalmology, Second Hospital of Jilin University, Jilin University, Changchun 130041, China. lhbswqw@126.com.|Department of Ophthalmology, China-Japan Union Hospital, Jilin University, Changchun 130031, China. lhbswqw@126.com.
Jing
J
Zhao
Department of Ophthalmology, Second Hospital of Jilin University, Jilin University, Changchun 130041, China. chaizg2008@163.com.
Yuan
Y
Yin
Department of Ophthalmology, Second Hospital of Jilin University, Jilin University, Changchun 130041, China. zhengyajuan124@126.com.
Yajuan
Y
Zheng
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000090007:CLC-2 Chloride Channels; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D003228:Conjunctiva / Q000166:cytology / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015290:Second Messenger Systems
D000199:Actins; D000090007:CLC-2 Chloride Channels; D018118:Chloride Channels; D024042:Collagen Type I; D005353:Fibronectins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
CLC-2 siRNA; TGF-β1 differentiation; extracellular matrix; human conjunctival fibroblasts; migration; signaling pathway