• BMB Reports
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• v.51 no.12
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• pp.648-653
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• 2018

Serine protease inhibitor Kazal type 1 (SPINK1) plays a role in protecting the pancreas against premature activation of trypsinogen and is involved in cancer progression. SPINK1 promoted LAC cells growth, migration, and invasion. Mechanistically, we found that SPINK1 promoted LAC cells migration and invasion via up-regulating matrix metalloproteinase 12 (MMP12). We observed that SPINK1 expression was only up-regulated in lung adenocarcinoma (LAC) tissues, and was an independent prognostic factor for poor survival. Our results indicate that SPINK1 might be a potential biomarker for LAC that promotes progression by MMP12.

• Journal of Ginseng Research
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• v.44 no.6
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• pp.799-807
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• 2020

Background: The skin acts as a barrier to protect organisms against harmful exogenous agents. Compound K (CK) is an active metabolite of ginsenoside Rb1, Rb2 and Rc, and researchers have focused on its skin protective efficacy. In this study, we hypothesized that increased expression of the serine protease inhibitor Kazal type-5 (SPINK5) may improve skin barrier function. Methods: We screened several ginsenosides to increase SPINK5 gene promoter activity using a transactivation assay and found that CK can increase SPINK5 expression. To investigate the protective effect of CK on the skin barrier, RT-PCR and Western blotting were performed to investigate the expression levels of SPINK5, kallikrein 5 (KLK5), KLK7 and PAR2 in UVB-irradiated HaCaT cells. Measurement of transepidermal water loss (TEWL) and histological changes associated with the skin barrier were performed in a UVB-irradiated mouse model and a 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis-like model. Results: CK treatment increased the expression of SPINK5 and decreased the expression of its downstream genes, such as KLKs and PAR2. In the UVB-irradiated mouse model and the DNCB-induced atopic dermatitis model, CK restored increased TEWL and decreased hydration and epidermal hyperplasia. In addition, CK normalized the reduced SPINK5 expression caused by UVB or DNCB, thereby restoring the expression of the proteins involved in desquamation to a level similar to normal. Conclusions: Our data showed that CK contributes to improving skin-barrier function in UVB-irradiated and DNCB-induced atopic dermatitis-like models through SPINK5. These results suggest that therapeutic attempts with CK might be useful in treating barrier-disrupted diseases.

• Journal of Digestive Cancer Reports
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• v.7 no.1
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• pp.18-21
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• 2019

Serine protease inhibitor Kazal-type 1 (SPINK1) is a gene expressed from pancreatic acinar cell which its mutation is known to be associated with chronic pancreatitis (CP) and pancreatic cancer. We report a case of a 47-years-old female with nausea and weight loss with yellow discoloration of skin. Initial imaging and endoscopic study led us to an impression of chronic pancreatitis with pancreatic cancer with common bile-duct dilation. Biopsy result was confirmed with pancreatic adenocarcinoma and additional imaging revealed lymph node and bone metastasis. Our genetic analysis revealed 194+2T>C mutation of SPINK1. Biliary obstruction was successfully decompressed by stent insertion and underwent chemotherapy and radiotherapy. Although there is accumulating evidence of association between SPINK1 mutation and CP, the relationship between SPINK1 mutation and pancreatic cancer in CP patient is an emerging concept. Genetic analysis should be considered in patients with young age especially when diagnosed with both CP and pancreatic cancer.

• Clinical and Experimental Pediatrics
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• v.56 no.5
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• pp.227-230
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• 2013

Chronic pancreatitis is a progressive inflammatory disease resulting from repeated episodes of acute pancreatitis that impair exocrine function and eventually produce endocrine insufficiency. Some causes of chronic pancreatitis appear to be associated with alterations in the serine-protease inhibitor, Kazal type 1 (SPINK1), cationic trypsinogen (PRSS1), and cystic fibrosis-transmembrane conductance regulator (CFTR ) genes, or with structural disorders in the pancreaticobiliary ductal system, such as pancreatic divisum or anomalous pancreaticobiliary ductal union (APBDU). However, it is unusual to observe both genetic alteration and structural anomaly. Here, we report 2 cases with both APBDU and a mutation in the SPINK1 genes, and we discuss the implications of these findings in clinical practice.