Hydrostatin-SN10 Ameliorates Pancreatitis-Induced Lung Injury by Affecting IL-6-Induced JAK2/STAT3-Associated Inflammation and Oxidative Stress
Authors: Qingyu Zhang
Xiaodan Sui
Baohai Liu
Tong Wu
Fanji Meng
Shuangdi Li
Yanping Zou
Chi Ma
Xuehua Piao
Journal: Oxidative Medicine and Cellular Longevity (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Hydrostatin-SN10; Pancreatitis; Acute lung injury; IL-6; JAK2/STAT3 pathway
Affiliations: Department of Traditional Chinese Medicine, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China., Department of Digestive Endoscopy, The Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun 130021, China., Internal Medicine of Traditional Chinese Medicine, The Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun 130021, China., Department of Gastroenterology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China., Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, China., Heart Disease Center, The Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun 130021, China.

Abstract:  Hydrostatin-SN1 (peptide sequence, DEQHLETELHTLTSVLTANGFQ), a kind of peptides extracted from snake venom, has been reported to have anti-inflammatory effect, but its truncated mutant hydrostatin-SN10 (peptide sequence, DEQHLETELH) on pancreatitis-induced acute lung injury has not been well documented. Interleukin- (IL-) 6-induced Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) pathway is involved with inflammatory and oxidative stress activities and may be associated with the pathogenesis of lung injury, and related molecules were measured. Taurocholate-induced pancreatitis associated with acute lung injury was established and treated with hydrostatin-SN10. Pancreatitis was confirmed by measuring the serum levels of amylase, lipase, and trypsinogen and urinary amylase. Lung injury was determined by histologically assessing acinar cell changes. The related molecules of IL-6-induced JAK2/STAT3-associated inflammation and oxidative stress were quantitated by real time-PCR, Western blot, and/or immunochemical assay. Hydrostatin-SN10 reduced the levels of serum amylase, lipase, and trypsinogen and urinary amylase when compared with the model group (p &lt; 0.05). Hydrostatin-SN10 significantly inhibited the IL-6-stimulated JAK2/STAT3 pathway and reduced the number of apoptotic cells via the downregulation of caspase 3 and BAX (proapoptotic) and upregulation of Bcl2 (antiapoptotic) (p &lt; 0.05). IL-6 induced the increase in the levels of JAK2 and STAT3, which was reversed by hydrostatin-SN10 treatment (p &lt; 0.05). In addition, hydrostatin-SN10 reduced the expression of IL-6 and TNF- (tumor necrosis factor-) Œ± and increased the level of IL-10 (p &lt; 0.05). On the other hand, hydrostatin-SN10 treatment increased the levels of superoxide dismutase (SOD) and reduced glutathione (GSH) and the levels of malondialdehyde (MDA) and alanine aminotransferase (ALT) (p &lt; 0.05). These results suggest that hydrostatin-SN10 may inhibit pancreatitis-induced acute lung injury by affecting IL-6-mediated JAK2/STAT3 pathway-associated inflammation and oxidative stress. 

Retracted: Yes

PubPeer comments:
 2021 retraction. https: www.hindawi.com journals omcl 2021 8541783 Oxidative Medicine and Cellular Longevity has retracted the article titled u201cHydrostatin-SN10 Ameliorates Pancreatitis-Induced Lung Injury by Affecting IL-6-Induced JAK2 STAT3-Associated Inflammation and Oxidative Stressu201d [1] at the request of the authors due to not acknowledging prior work and errors in the analysis. Hydrostatin-SN10, derived from Hydrostatin-SN1, was previously described in two Masteru2019s theses that were not cited [2, 3]. Patents held by Yiming Lu and colleagues [4, 5] were not acknowledged and the peptide supplier had a confidentiality agreement with Dr. Lu. The KD value for SN10 given in the introduction has the wrong unit (u03bc versus u03bcM) and cannot be relied upon because it was not validated by the use of surface plasmon resonance (SPR) analysis [6] or isothermal titration calorimetry (ITC) [7]. Two control groups should have been included, as noted in [8]: a positive control in the group treated by the SN10 mutant and a negative control in the group treated by the unrelated octapeptide, otherwise the results cannot be stated to have been specifically caused by SN10 treatment. Similar results may be induced by other decapeptides (for example, see [9u201311]). The authors apologized and the editorial board approved the retraction. References X. Piao, Y. Zou, X. Sui et al., u201cHydrostatin-SN10 Ameliorates Pancreatitis-Induced Lung Injury by Affecting IL-6-Induced JAK2 STAT3-Associated Inflammation and Oxidative Stress,u201d Oxidative Medicine and Cellular Longevity, vol. 2019, Article ID 9659757, 12 pages, 2019. H. Jiang, Structural optimization and anti-inflammatory mechanism of the anti-inflammatory peptide Hydrostatin-SN1 from sea snake venom [Masteru2019s thesis], Second Military Medical University, 2016. Y. Bian, The preliminary pharmacodynamic study of selective TNFR1 antagonist peptide Hydrostatin-SN10 in the treatment of inflammatory bowel disease [Masteru2019s thesis], Shanghai Normal University, 2017. Y. Lu, J. Wang, A. Li et al., u201cApplication of Selection TNFR1 Antagonist Peptide SN10 in Preparation of Drugs for Preventing and Treating Rheumatoid Arthritis,u201d 2018, https: patents.google.com patent US20200188471A1 en. Y. Lu, H. Jiang, Y. Bian et al., u201cSelective TNFR1 Antagonist Peptide SN10 and Application Thereof in Inflammatory Bowel Disease,u201d 2018, https: patents.google.com patent US20200277355A1 en. View at: Google Scholar H. Tachibana, K. Koga, Y. Fujimura, and K. Yamada, u201cA receptor for green tea polyphenol EGCG,u201d Nature Structural Molecular Biology, vol. 11, no. 4, pp. 380-381, 2004. A. Mouru00e3o, A. R. Nager, M. V. Nachury, and E. Lorentzen, u201cStructural basis for membrane targeting of the BBSome by ARL6,u201d Nature Structural Molecular Biology, vol. 21, no. 12, pp. 1035u20131041, 2014. K. Hilpert and R. E. W. Hancock, u201cUse of luminescent bacteria for rapid screening and characterization of short cationic antimicrobial peptides synthesized on cellulose using peptide array technology,u201d Nature Protocols, vol. 2, no. 7, pp. 1652u20131660, 2007. K. Sowmya, M. I. Bhat, R. K. Bajaj, S. Kapila, and R. Kapila, u201cBuffalo Milk Casein Derived Decapeptide (YQEPVLGPVR) Having Bifunctional Anti-inflammatory and Antioxidative Features Under Cellular Milieu,u201d International Journal of Peptide Research and Therapeutics, vol. 25, no. 2, pp. 623u2013633, 2019. M. Namba, M. A. Ghatei, M. Ghiglione, and S. R. Bloom, u201cEffects of decapeptide of mammalian bombesin and neuromedin B on pancreatic exocrine secretion in the rat,u201d Digestion, vol. 34, no. 2, pp. 105u2013114, 1986. A. Bourreille, M. Doubremelle, D. R. de la Blu00e9tiu00e8re et al., u201cRDP58, a novel immunomodulatory peptide with anti-inflammatory effects. A pharmacological study in trinitrobenzene sulphonic acid colitis and Crohn disease,u201d Scandinavian Journal of Gastroenterology, vol. 38, no. 5, pp. 526u2013532, 2003. ,