TY - JOUR
T1 - SPOCK1 is a novel inducer of epithelial to mesenchymal transition in drug-induced gingival overgrowth
AU - Alshargabi, Rehab
AU - Sano, Tomomi
AU - Yamashita, Akiko
AU - Takano, Aiko
AU - Sanada, Taiki
AU - Iwashita, Misaki
AU - Shinjo, Takanori
AU - Fukuda, Takao
AU - Sanui, Terukazu
AU - Kishida, Shosei
AU - Nishimura, Fusanori
N1 - Funding Information:
This study was supported by Grant-in-Aid from Japan Society for the Promotion of Science (No. 16H05555, 18K09578, 19K22721). We would like to thank Reiko U. Yoshimoto for her kind advices and we appreciate the technical assistance from Megumi Kiyota and other staff at The Research Support Center, Research Center for Human Disease Modeling, Kyushu University Graduate School of Medical Sciences.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Few studies have investigated the role of extracellular-matrix proteoglycans in the pathogenesis of drug-induced gingival overgrowth (DIGO). SPOCK1 is an extracellular proteoglycan that induces epithelial to mesenchymal transition (EMT) in several cancer cell lines and exhibits protease-inhibitory activity. However, the role of SPOCK1 in non-cancerous diseases such as DIGO has not been well-addressed. We demonstrated that the expression of SPOCK1, TGF-β1, and MMP-9 in calcium channel blocker-induced gingival overgrowth is higher than that in non-overgrowth tissues. Transgenic mice overexpressing Spock1 developed obvious gingival-overgrowth and fibrosis phenotypes, and positively correlated with EMT-like changes. Furthermore, in vitro data indicated a tri-directional interaction between SPOCK1, TGF-β1, and MMP-9 that led to gingival overgrowth. Our study shows that SPOCK1 up-regulation in a noncancerous disease and SPOCK1-induced EMT in gingival overgrowth occurs via cooperation and crosstalk between several potential signaling pathways. Therefore, SPOCK1 is a novel therapeutic target for gingival overgrowth and its expression is a potential risk of EMT induction in cancerous lesions.
AB - Few studies have investigated the role of extracellular-matrix proteoglycans in the pathogenesis of drug-induced gingival overgrowth (DIGO). SPOCK1 is an extracellular proteoglycan that induces epithelial to mesenchymal transition (EMT) in several cancer cell lines and exhibits protease-inhibitory activity. However, the role of SPOCK1 in non-cancerous diseases such as DIGO has not been well-addressed. We demonstrated that the expression of SPOCK1, TGF-β1, and MMP-9 in calcium channel blocker-induced gingival overgrowth is higher than that in non-overgrowth tissues. Transgenic mice overexpressing Spock1 developed obvious gingival-overgrowth and fibrosis phenotypes, and positively correlated with EMT-like changes. Furthermore, in vitro data indicated a tri-directional interaction between SPOCK1, TGF-β1, and MMP-9 that led to gingival overgrowth. Our study shows that SPOCK1 up-regulation in a noncancerous disease and SPOCK1-induced EMT in gingival overgrowth occurs via cooperation and crosstalk between several potential signaling pathways. Therefore, SPOCK1 is a novel therapeutic target for gingival overgrowth and its expression is a potential risk of EMT induction in cancerous lesions.
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U2 - 10.1038/s41598-020-66660-z
DO - 10.1038/s41598-020-66660-z
M3 - Article
C2 - 32555336
AN - SCOPUS:85086579836
SN - 2045-2322
VL - 10
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 9785
ER -
