Ulcer‐associated cell lineage expresses genes involved in regeneration and is hallmarked by high neutrophil gelatinase‐associated lipocalin (NGAL) levels

Thorsvik, Silje; Granlund, Atle van Beelen; Svendsen, Tarjei Dahl; Bakke, Ingrid; Røyset, Elin Synnøve; Flo, Trude Helen; Damås, Jan Kristian; Østvik, Ann Elisabet; Sandvik, Arne K.

doi:10.1002/path.5258

Cited by 16 publications

(16 citation statements)

References 41 publications

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“…On this basis, it is highly likely that ticks inject host α1-antitrypsin and α2-macroglobulin into the feeding site as a strategy of evading the host’s tissue repair defense response. It is also notable that fibrinogen and neutrophil gelantinase-associated lipocalin, which among other functions plays important roles in wound healing, were identified towards the end of feeding (150–153). This is interesting in that the tick-feeding lesion is completely sealed, preventing leakage of blood, when a replete fed tick detaches from its feeding site.…”

Section: Resultsmentioning

confidence: 99%

Time-resolved proteomic profile ofAmblyomma americanumtick saliva during feeding

Kim

Tirloni

Pinto

et al. 2019

Preprint

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24Amblyomma americanum ticks transmit more than a third of human tick-borne disease 25 (TBD) agents in the United States. Tick saliva proteins are critical to success of ticks as vectors 26 of TBD agents, and thus might serve as targets in tick antigen-based vaccines to prevent TBD 27 infections. We describe a systems biology approach to identify, by LC-MS/MS, saliva proteins 28 (tick=1182, rabbit=335) that A. americanum ticks likely inject into the host every 24 h during the 29 first 8 days of feeding, and towards the end of feeding using two different sample preparation 30 approaches (in-gel and in-solution). The in-gel approach determined molecular identification of 31 predominant protein bands in tick saliva, and the in-solution added depth to discovery of 32 proteins. Searching against entries in GenBank grouped tick and rabbit proteins in this study into 33 27 and 25 functional categories. Aside from housekeeping-like proteins, majority of tick saliva 34 proteins belong to the tick-specific (no homology to non-tick organisms: 32%), protease 35 inhibitors (13%), proteases (8%), glycine-rich proteins (6%) and lipocalins (4%) categories.36 Global secretion dynamics analysis suggests that majority (74%) of proteins in this study are 37 associated with regulating initial tick feeding functions and transmission of pathogens as they are 38 secreted within 24-48 h of tick attachment. Comparative analysis of the A. americanum tick 39 saliva proteome to five other tick saliva proteomes identified 284 conserved tick saliva proteins:40 we speculate that these regulate critical tick feeding functions and might serve as tick vaccine 41 antigens. We discuss our findings in the context of understanding A. americanum tick feeding 42 physiology as a means through which we can find effective targets for a vaccine against tick 43 feeding. 44 45 3 46 Author Summary 47The lone star tick, Amblyomma americanum, is a medically important species in US that 48 transmits 5 of the 16 reported tick-borne disease agents. Most recently, bites of this tick were 49 associated with red meat allergies in humans. Vaccination of animals against tick feeding has 50 been shown to be a sustainable and effective alternative to current acaricide based tick control 51 method which has several limitations. The pre-requisite to tick vaccine development is to 52 understand the molecular basis of tick feeding physiology. Toward this goal, this study has 53 identified proteins that A. americanum ticks inject into the host at different phases of its feeding 54 cycle. This data set has identified proteins that A. americanum inject into the host within 24-48 h 55 of feeding before it starts to transmit pathogens. Of high importance, we identified 284 proteins 56 that are present in saliva of other tick species, which we suspect regulate important role(s) in tick 57 feeding success and might represent rich source target antigens for a tick vaccine. Overall, this 58 study provides a foundation to understand the molecular mechanisms regulating tick feeding 59 p...

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Section: Resultsmentioning

confidence: 99%

Time-resolved proteomic profile ofAmblyomma americanumtick saliva during feeding

Kim

Tirloni

Pinto

et al. 2019

Preprint

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“…LCM was performed as previously described. 27 Briefly, samples were cut into 10-µm sections and mounted on RNAse-free MMI Membrane Slides [Molecular Machines and Industry, MMI]; samples were then stained with haematoxylin following standard protocols. The sections were dehydrated with 100% ethanol and xylenes, followed by air-drying in a desiccator for at least 30 min.…”

Section: Methodsmentioning

confidence: 99%

The Water Channel Aquaporin 8 is a Critical Regulator of Intestinal Fluid Homeostasis in Collagenous Colitis

Escudero-Hernández

Münch

Østvik

et al. 2020

Journal of Crohn's and Colitis

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Background and Aims Diarrhoea is a common, debilitating symptom of gastrointestinal disorders. Pathomechanisms probably involve defects in trans-epithelial water transport, but the role of aquaporin [AQP] family water channels in diarrhoea-predominant diseases is unknown. We investigated the involvement of AQPs in the pathobiology of collagenous colitis [CC], which features chronic, watery diarrhoea despite overtly normal intestinal epithelial cells [IECs]. Methods We assessed the expression of all AQP family members in mucosal samples of CC patients before and during treatment with the corticosteroid drug budesonide, steroid-refractory CC patients and healthy controls. Samples were analysed by genome-wide mRNA sequencing [RNA-seq] and quantitative real-time PCR [qPCR]. In some patients, we performed tissue microdissection followed by RNA-seq to explore the IEC-specific CC transcriptome. We determined changes in the protein levels of the lead candidates in IEC by confocal microscopy. Finally, we investigated the regulation of AQP expression by corticosteroids in model cell lines. Results Using qPCR and RNA-seq, we identified loss of AQP8 expression as a hallmark of active CC, which was reverted by budesonide treatment in steroid-responsive but not refractory patients. Consistently, decreased AQP8 mRNA and protein levels were observed in IECs of patients with active CC, and steroid drugs increased AQP8 expression in model IECs. Moreover, low APQ8 expression was strongly associated with higher stool frequency in CC patients. Conclusion Down-regulation of epithelial AQP8 may impair water resorption in active CC, resulting in watery diarrhoea. Our results suggest that AQP8 is a potential drug target for the treatment of diarrhoeal disorders.

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“…Experimental kidney injury (KI) animal models are very helpful in screening potential nephrotoxic reagents and possible anti-KI compounds in vivo, and they also can provide research tools to study renal pathophysiology. However, traditional biomarkers measuring renal functions in the human study, such as blood urea nitrogen (BUN) and serum creatinine (Scr), are not sensitive enough to detect early or slight damages in experimental animals [ 1 , 2 ]. Urine-derived biomarkers such as albumin, vanin-1, N-acetyl-β- d -glucosamininidase, and kidney injury molecule-1 might be effective biomarkers [ 3 , 4 ]; however, in some conditions, especially when a large number of animals are used in the same experiment batch, serum-derived KI biomarkers might be more advantageous becaue of their shorter identification time and simple extraction.…”

Section: Introductionmentioning

confidence: 99%

Prediction Value of Serum NGAL in the Diagnosis and Prognosis of Experimental Acute and Chronic Kidney Injuries

Wang

Chen

et al. 2020

Biomolecules

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Sensitive and accurate serum biomarkers for monitoring acute and chronic kidney disease progression are more convenient and can better evaluate drug efficiency in pharmacological research. Neutrophil Gelatinase-associated Lipocalin (NGAL) is considered a hopeful early biomarker of acute kidney injury (AKI), but its utility in early prediction and prognosis of diabetic nephropathy (DN) and immune-mediated glomerulonephritis is still not clear. Moreover, detailed prognosis studies of NGAL in AKI are lacking, and most studies use a urine source. In the current study, through two experimental AKI and two chronic kidney injury animal models, serum NGAL (sNGAL) prediction values on diagnosis and prognosis of kidney injuries in animal disease models have been investigated thoroughly. Four experimental kidney disease models include cisplatin-induced and lipopolysaccharide (LPS)-induced AKI, streptozocin-induced diabetic nephropathy (DN), and cationized-bovine serum albumin (c-BSA)-induced membranous nephropathy (MN), respectively. The sNGAL concentration was measured at different stages of kidney injury (KI) in each experimental model, and receiver operating characteristic (ROC) analyses were performed to investigate the diagnosis efficiency of sNGAL for KI. Western blot and immunohistochemistry were used to measure the protein levels in the kidneys, and pathological analysis was used as the gold standard to confirm KI. Results suggest that sNGAL can predict early diagnosis of cisplatin-induced AKI accurately but is less powerful in later stages compared to blood urea nitrogen (BUN) and serum creatinine (Scr). sNGAL is sensitive but lacks specificity to evaluate early kidney injury for LPS-induced AKI under low-dosage LPS challenge. sNGAL is not an efficient biomarker for early diagnosis of STZ-induced DN, but sNGAL is an efficient predictor for the early diagnosis and prognosis of immune-mediated MN. In conclusion, application of sNGAL as a kidney injury biomarker to determine the diagnosis and prognosis in pharmacological studies is dependent on experimental animal models.

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Ulcer‐associated cell lineage expresses genes involved in regeneration and is hallmarked by high neutrophil gelatinase‐associated lipocalin (NGAL) levels

Cited by 16 publications

References 41 publications

Time-resolved proteomic profile ofAmblyomma americanumtick saliva during feeding

Time-resolved proteomic profile ofAmblyomma americanumtick saliva during feeding

The Water Channel Aquaporin 8 is a Critical Regulator of Intestinal Fluid Homeostasis in Collagenous Colitis

Prediction Value of Serum NGAL in the Diagnosis and Prognosis of Experimental Acute and Chronic Kidney Injuries

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