The Inhibition of Inflammatory Signaling Pathway by Secretory Leukocyte Protease Inhibitor can Improve Spinal Cord Injury

Tang, Renzhe; Botchway, Benson O. A.; Meng, Yanfeng; Zhang, Yong; Conghui, Zhou; Jiang, Junsong; Liu, Xuehong

doi:10.1007/s10571-020-00799-1

Cited by 28 publications

(20 citation statements)

References 69 publications

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“…SLPI, secretory leukocyte peptidase inhibitor，among the top 5 DEGs up-regulated by CASP3 siRNA (Table 3), was renoprotective in experimental ischemia AKI (Ochi et al, 2017). SLPI inhibits nuclear factor kappa beta (NF-κB) signaling pathway (Tang et al, 2020) and the maturation of IL-1β (Zakrzewicz et al, 2019), and showed as a biomarker candidate in AKI (Averdunk et al, 2019;Averdunk et al, 2020). In human, SERPINA3, a member of the serpin superfamily of protease inhibitors, could limit inflammation by targeting cathepsin family (proinflammatory enzymes) (Horvath et al, 2005;Lannan et al, 2012).…”

Section: Downloaded Frommentioning

confidence: 99%

Potent Therapy and Transcriptional Profile of Combined Erythropoietin-Derived Peptide Cyclic Helix B Surface Peptide and Caspase-3 siRNA against Kidney Ischemia/Reperfusion Injury in Mice

Chen

Zhang

et al. 2020

J Pharmacol Exp Ther

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Caspase-3 siRNA CASP3siRNA, targeting murine caspase-3 mRNA (NCBI CoreNucleotide Accession No. BC038825), were synthesized (Life Technologies, Paisley, UK). The sequences of the CASP3siRNA (Ambion In Vivo, catalogue number: 4457309) were sense 5'-CCUGGUUACUAUUCCUGGAtt-3' and antisense 5'-UCCAGGAAUAGUAACCAGGtg-3'. The negative control siRNA (NCsiRNA) was also provided by Life Technologies (Ambion In Vivo, catalogue number: 4457289), with sequences of sense 5'-UAACGACGCGACGACGUAAtt-3' and antisense 5'-UUACGUCGUCGCGUCGUUAtt-3'. Both CASP3siRNA and NCsiRNA were chemically modified by locked nuclei acid. Renal IR surgery Male C57BL/6 mice, 8-12 weeks, were purchased from the Experimental Animal Center of Yangzhou University, China. All animal experiments were performed according to the guidelines of the Laboratory Animal Monitoring Committee of Jiangsu Province.

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Section: Downloaded Frommentioning

confidence: 99%

Potent Therapy and Transcriptional Profile of Combined Erythropoietin-Derived Peptide Cyclic Helix B Surface Peptide and Caspase-3 siRNA against Kidney Ischemia/Reperfusion Injury in Mice

Chen

Zhang

et al. 2020

J Pharmacol Exp Ther

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“…SLPI, secretory leukocyte peptidase inhibitor among the top 5 DEGs up-regulated by CASP3 siRNA (Table 3), was renoprotective in experimental ischemia AKI (Ochi et al, 2017). SLPI inhibits nuclear factor kappa beta (NF-κB) signaling pathway (Tang et al, 2020) and the maturation of IL-1β (Zakrzewicz et al, 2019), and showed as a biomarker candidate in AKI (Averdunk et al, 2019;Averdunk et al, 2020). In human, SERPINA3, a member of the serpin superfamily of protease inhibitors, could limit in ammation by targeting cathepsin family (proin ammatory enzymes) (Horvath et al, 2005;Lannan et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Potent Therapy and Transcriptional Profile of Combined Erythropoietin Derived Peptide CHBP and Caspase-3 siRNA against Kidney Ischemia/Reperfusion Injury in mice

Wu¹,

Chen²,

Zhang³

et al. 2020

Preprint

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Cause-specific treatment and timely diagnosis are still not available for acute kidney injury (AKI) apart from supportive therapy and serum creatinine measurement. A novel erythropoietin-derived cyclic helix B surface peptide (CHBP) protects kidneys against AKI with different causes, but the underlying mechanism is not fully defined. Herein, we investigated the transcriptional profile of renoprotection induced by CHBP and its potential synergistic effects with siRNA targeting caspase-3, an executing enzyme of apoptosis and inflammation, (CASP3siRNA) on ischemia/reperfusion (IR)-induced AKI. Utilizing a mouse model with 30-min renal bilateral ischemia and 48-h reperfusion, the renoprotection of CHBP or CASP3siRNA was demonstrated in renal function and structure, active caspase-3 and HMGB1 expression. Combined treatment of CHBP and CASP3siRNA further preserved kidney structure, and reduced active caspase-3 and HMGB1. Furthermore, differentially expressed genes (DEGs) were identified with fold change > 1.414 and P < 0.05. In IR kidneys, 281 DEGs induced by CHBP were mainly involved in promoting cell division and improving cellular function and metabolism (up-regulated STAT5B and SLC22A7). The additional administration of CASP3siRNA caused 504 and 418 DEGs in IR + CHBP kidneys with or without NCsiRNA, with 37 genes in common. These DEGs were associated with modulated apoptosis and inflammation (up-regulated BCL6, SLPI and SERPINA3M), and immunity, injury and microvascular homeostasis (up-regulated CFH and GREM1, and down-regulated ANGPTL2). This proof-of-effect study indicated the potent renoprotection of CASP3siRNA upon CHBP at the early stage of IR-induced AKI. Underlying genes, BCL6, SLPI, SERPINA3M, GREM1 and ANGPTL2, might be potential new biomarkers for clinical applications.

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“…There may be differentiations between (Table 3), was renoprotective in experimental ischemia AKI [38]. SLPI inhibits nuclear factor kappa beta (NF-κB) signaling pathway [39] and the maturation of IL-1β [40], and shown as a biomarker candidate in AKI [41,42]. In human, SERPINA3, a member of the serpin superfamily of protease inhibitors, could limit inflammation by targeting cathepsin family (proinflammatory enzymes) [43,44].…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Profiles in Ischemia/Reperfusion-Injured Murine Kidneys Synergistically Protected by Erythropoietin Derived Peptide CHBP and Caspase-3 siRNA

Chen

Zhang

et al. 2020

Preprint

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Background: Target-specific treatment is not available for acute kidney injury (AKI). A novel erythropoietin-derived cyclic helix B surface peptide (CHBP) protects kidneys against AKI subjected to different causes. Herein, we investigated the transcriptional profile of renoprotection induced by CHBP and its potential synergistic effects with caspase-3 siRNA (CASP3siRNA) on ischemia/reperfusion (IR) injury associated AKI. Methods: A mouse renal IR model was established by clamping bilateral pedicles for 30 min and reperfusion for 48 h. 0.03 mg/kg of CASP3siRNA/negative control (NCsiRNA) was injected via tail vein 2 h pre-surgery, with/without 24 nmol/kg of CHBP administered to peritoneal cavity at 15 min post reperfusion. The transcriptomic profile in kidneys was assessed by affymetrix gene chips, along with renal function, histology, active caspase-3 and HMGB1.Results: CHBP or CASP3siRNA significantly improved renal function and structure, with decreased caspase-3 and HMGB1 in IR kidneys. Combined treatment of CHBP and CASP3siRNA further preserved kidney structure, and reduced active caspase-3 and HMGB1. Furthermore, fold change > 1.414 and P < 0.05 were used to identify differentially expressed genes (DEGs). In IR kidneys, 281 DEGs induced by CHBP were mainly involved in promoting cell division and improving cellular function and metabolism (up-regulated STAT5B and SLC22A7). The additional administration of CASP3siRNA caused 504 and 418 DEGs in IR + CHBP kidneys with or without NCsiRNA, with 37 genes in common. These DEGs were associated with modulated apoptosis and inflammation (up-regulated BCL6，SLPI and SERPINA3M), and immunity, injury and microvascular homeostasis (up-regulated CFH and GREM1, and down-regulated ANGPTL2). Conclusions: This proof-of-effect study indicated that the synergistic renoprotection of CHBP and CASP3siRNA at the early stage of IR-induced AKI. Underlying genes, BCL6, SLPI, SERPINA3M, GREM1 and ANGPTL2, might be potential new biomarkers for clinical applications.

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The Inhibition of Inflammatory Signaling Pathway by Secretory Leukocyte Protease Inhibitor can Improve Spinal Cord Injury

Cited by 28 publications

References 69 publications

Potent Therapy and Transcriptional Profile of Combined Erythropoietin-Derived Peptide Cyclic Helix B Surface Peptide and Caspase-3 siRNA against Kidney Ischemia/Reperfusion Injury in Mice

Potent Therapy and Transcriptional Profile of Combined Erythropoietin-Derived Peptide Cyclic Helix B Surface Peptide and Caspase-3 siRNA against Kidney Ischemia/Reperfusion Injury in Mice

Potent Therapy and Transcriptional Profile of Combined Erythropoietin Derived Peptide CHBP and Caspase-3 siRNA against Kidney Ischemia/Reperfusion Injury in mice

Transcriptional Profiles in Ischemia/Reperfusion-Injured Murine Kidneys Synergistically Protected by Erythropoietin Derived Peptide CHBP and Caspase-3 siRNA

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