当前位置： SCI文献检索 > JOURNAL OF PERIODONTAL RESEARCH期刊下所有文献 > Activated KCNQ1 channel promotes fibrogenic response in hereditary gingival fibromatosis via clustering and activation of Ras.

Activated KCNQ1 channel promotes fibrogenic response in hereditary gingival fibromatosis via clustering and activation of Ras.

Abstract：

BACKGROUND AND OBJECTIVE:Activated potassium channels were found to be strongly correlated with gingival overgrowth (GO) phenotype as we reviewed syndromic hereditary gingival fibromatosis (HGF). Nevertheless, the functional roles of potassium channels in gingival fibrosis or gingival overgrowth remained uncovered. The aim of the present study was to explore the pathogenic role of aberrantly activated potassium channel in Hereditary Gingival Fibromatosis (HGF). METHODS:Gingival tissues were collected from 9 HGF patients and 15 normal controls. Expression of KCNQ1 was detected by immunohistochemistry. Gingival fibroblasts were isolated, and outward K+ currents were detected by whole-cell patch-clamp analysis, transmembrane potential was determined by flow cytometry. Normal human gingival fibroblasts (NHGFs) were transfected with KCNQ1 adenovirus or treated with KCNQ1 selective agonist ML277 and antagonist chromanol 293B. Accumulation of Extracellular Matrix (ECM) was measured by Western blotting and Sircol Soluble Collagen Assay. Content of secreted TGF-β1 was measured by ELISA. Active RAS pull-down assay and cell immunofluorescence were utilized to verify RAS activation. RESULTS:KCNQ1 was upregulated in gingival tissues derived from HGF patients and HGF gingival fibroblasts presented increased outward K+ currents than NHGFs. Overexpression of KCNQ1, or KCNQ1 agonist ML277, promoted fibrotic responses of NHGFs. TGF-β1 and KCNQ1 channels formed a positive feed-back loop. ML277 generated lateral clustering and activation of Ras on plasma membrane, followed by augmented MAPK/AP-1 signaling pathway output. JNK or ERK1/2 inhibitors suppressed ML277-induced AP-1 and ECM upregulation. CONCLUSION:Activation of KCNQ1 potassium channel promoted fibrogenic responses in NHGFs via Ras/MAPK/AP-1 signaling.

journal_name

J Periodontal Res

journal_title

Journal of periodontal research

authors

Gao Q,Yang C,Meng L,Wang Z,Chen D,Peng Y,Yang K,Bian Z

doi

10.1111/jre.12836

subject

Has Abstract

pub_date

2020-12-31 00:00:00

eissn

0022-3484

issn

1600-0765

pub_type

杂志文章

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Activated KCNQ1 channel promotes fibrogenic response in hereditary gingival fibromatosis via clustering and activation of Ras.