Abstract
Diabetes mellitus is a complex and heterogeneous disease, which has β-cell dysfunction at its core. Glucotoxicity affects pancreatic islets, causing β-cell apoptosis. However, the role of JNK/β-catenin signaling in glucotoxic β-cell apoptosis is not well understood. Recently, we identified tetraspanin-2 (TSPAN2) protein as a proapoptotic β-cell factor induced by glucose, suggesting that TSPAN2 might contribute to pancreatic β-cell glucotoxicity. To investigate the effects of glucose concentration on TSPAN2 expression and apoptosis, we used reverted immortalizedRNAKT-15 human pancreatic β cells.High TSPAN2 levels up-regulated phosphorylated (p) JNK and induced apoptosis. p-JNK enhanced the phosphorylation of b-catenin and Dickkopf-1 (Dkk1). Dkk1 knockdownbysmall interfering (si)RNAup-regulated nuclearb-catenin, suggestingthat it isaJNK/β-catenin-dependent pathway. siRNA-mediatedTSPAN2depletion inRNAKT-15 cells increased nuclearb-catenin.ThisdecreasedBCL2- associated X protein (Bax) activation, leading to marked protection against high glucose-induced apoptosis. Bax subfamily proteins induced apoptosis through caspase-3. Thus, TSPAN2might have induced Bax translocation and caspase-3 activation in pancreatic β cells, thereby promoting the apoptosis ofRNAKT-15 cells by regulating the JNK/ b-catenin pathway in response to high glucose concentrations. Targeting TSPAN2 could be a potential therapeutic strategy to treat glucose toxicity-inducedβ-cell failure.-Hwang, I.-H., Park, J., Kim,J.M., Kim,S. I.,Choi, J.-S.,Lee, K.-B., Yun, S. H., Lee, M.-G., Park, S. J., Jang, I.-S. Tetraspanin-2 promotes glucotoxic apoptosis by regulating the JNK/β-catenin signaling pathway in human pancreatic β cells.
| Original language | English |
|---|---|
| Pages (from-to) | 3107-3116 |
| Number of pages | 10 |
| Journal | FASEB Journal |
| Volume | 30 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 2016 Sep 1 |
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Keywords
- Bax
- Glucose toxicity
- TSPAN2
ASJC Scopus subject areas
- Biotechnology
- Biochemistry
- Molecular Biology
- Genetics
Cite this
Tetraspanin-2 promotes glucotoxic apoptosis by regulating the JNK/β-catenin signaling pathway in human pancreatic β cells. / Hwang, In Hu; Park, Junsoo; Kim, Jung Min; Il Kim, Seung; Choi, Jong Soon; Lee, Kyung Bok; Yun, Sung Ho; Lee, Min-Goo; Park, Soo Jung; Jang, Ik Soon.
In: FASEB Journal, Vol. 30, No. 9, 01.09.2016, p. 3107-3116.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Tetraspanin-2 promotes glucotoxic apoptosis by regulating the JNK/β-catenin signaling pathway in human pancreatic β cells
AU - Hwang, In Hu
AU - Park, Junsoo
AU - Kim, Jung Min
AU - Il Kim, Seung
AU - Choi, Jong Soon
AU - Lee, Kyung Bok
AU - Yun, Sung Ho
AU - Lee, Min-Goo
AU - Park, Soo Jung
AU - Jang, Ik Soon
PY - 2016/9/1
Y1 - 2016/9/1
N2 - Diabetes mellitus is a complex and heterogeneous disease, which has β-cell dysfunction at its core. Glucotoxicity affects pancreatic islets, causing β-cell apoptosis. However, the role of JNK/β-catenin signaling in glucotoxic β-cell apoptosis is not well understood. Recently, we identified tetraspanin-2 (TSPAN2) protein as a proapoptotic β-cell factor induced by glucose, suggesting that TSPAN2 might contribute to pancreatic β-cell glucotoxicity. To investigate the effects of glucose concentration on TSPAN2 expression and apoptosis, we used reverted immortalizedRNAKT-15 human pancreatic β cells.High TSPAN2 levels up-regulated phosphorylated (p) JNK and induced apoptosis. p-JNK enhanced the phosphorylation of b-catenin and Dickkopf-1 (Dkk1). Dkk1 knockdownbysmall interfering (si)RNAup-regulated nuclearb-catenin, suggestingthat it isaJNK/β-catenin-dependent pathway. siRNA-mediatedTSPAN2depletion inRNAKT-15 cells increased nuclearb-catenin.ThisdecreasedBCL2- associated X protein (Bax) activation, leading to marked protection against high glucose-induced apoptosis. Bax subfamily proteins induced apoptosis through caspase-3. Thus, TSPAN2might have induced Bax translocation and caspase-3 activation in pancreatic β cells, thereby promoting the apoptosis ofRNAKT-15 cells by regulating the JNK/ b-catenin pathway in response to high glucose concentrations. Targeting TSPAN2 could be a potential therapeutic strategy to treat glucose toxicity-inducedβ-cell failure.-Hwang, I.-H., Park, J., Kim,J.M., Kim,S. I.,Choi, J.-S.,Lee, K.-B., Yun, S. H., Lee, M.-G., Park, S. J., Jang, I.-S. Tetraspanin-2 promotes glucotoxic apoptosis by regulating the JNK/β-catenin signaling pathway in human pancreatic β cells.
AB - Diabetes mellitus is a complex and heterogeneous disease, which has β-cell dysfunction at its core. Glucotoxicity affects pancreatic islets, causing β-cell apoptosis. However, the role of JNK/β-catenin signaling in glucotoxic β-cell apoptosis is not well understood. Recently, we identified tetraspanin-2 (TSPAN2) protein as a proapoptotic β-cell factor induced by glucose, suggesting that TSPAN2 might contribute to pancreatic β-cell glucotoxicity. To investigate the effects of glucose concentration on TSPAN2 expression and apoptosis, we used reverted immortalizedRNAKT-15 human pancreatic β cells.High TSPAN2 levels up-regulated phosphorylated (p) JNK and induced apoptosis. p-JNK enhanced the phosphorylation of b-catenin and Dickkopf-1 (Dkk1). Dkk1 knockdownbysmall interfering (si)RNAup-regulated nuclearb-catenin, suggestingthat it isaJNK/β-catenin-dependent pathway. siRNA-mediatedTSPAN2depletion inRNAKT-15 cells increased nuclearb-catenin.ThisdecreasedBCL2- associated X protein (Bax) activation, leading to marked protection against high glucose-induced apoptosis. Bax subfamily proteins induced apoptosis through caspase-3. Thus, TSPAN2might have induced Bax translocation and caspase-3 activation in pancreatic β cells, thereby promoting the apoptosis ofRNAKT-15 cells by regulating the JNK/ b-catenin pathway in response to high glucose concentrations. Targeting TSPAN2 could be a potential therapeutic strategy to treat glucose toxicity-inducedβ-cell failure.-Hwang, I.-H., Park, J., Kim,J.M., Kim,S. I.,Choi, J.-S.,Lee, K.-B., Yun, S. H., Lee, M.-G., Park, S. J., Jang, I.-S. Tetraspanin-2 promotes glucotoxic apoptosis by regulating the JNK/β-catenin signaling pathway in human pancreatic β cells.
KW - Bax
KW - Glucose toxicity
KW - TSPAN2
UR - http://www.scopus.com/inward/record.url?scp=84990852792&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84990852792&partnerID=8YFLogxK
U2 - 10.1096/fj.201600240RR
DO - 10.1096/fj.201600240RR
M3 - Article
C2 - 27247127
AN - SCOPUS:84990852792
VL - 30
SP - 3107
EP - 3116
JO - The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
JF - The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
SN - 1530-6860
IS - 9
ER -