Furosemide-induced systemic dehydration alters the proteome of rabbit vocal folds

Nascimento, Naíla Cannes do; Santos, Andrea Pires dos; Mohallem, Rodrigo; Aryal, Uma K.; Xie, Jun; Cox, Abigail; Sivasankar, M. Preeti

doi:10.1016/j.jprot.2021.104431

Cited by 7 publications

(17 citation statements)

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“…The number of proteins identified in this study represents an increment of 602 vocal fold proteins compared to our previous study using 6-month-old rabbits (young) subjected to systemic dehydration with furosemide, which identified 1684 proteins [ 30 ]. This difference can be due to the different number of biological replicates used in each study, eight rabbits in the furosemide study versus 22 rabbits in the present study, and the filtering criteria applied in each study.…”

Section: Discussionmentioning

confidence: 92%

“…In addition to clinical and experimental studies, research focused on the underlying molecular mechanisms of hydration has shown that systemic dehydration affected gene and protein expression in the vocal folds of different animal models [ 28 – 30 ]. Transcriptome studies of the vocal folds from furosemide-induced systemically dehydrated rabbits revealed hundreds of differentially expressed genes compared with euhydrated rabbits [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

“…In that study, epithelial and cell adhesion-related genes were downregulated, suggesting systemic dehydration may perturb the vocal fold epithelium. Proteomic studies using the same rabbit model revealed dozens of differentially regulated proteins and suggested novel molecular evidence for increased susceptibility to oxidative stress [ 30 ] as observed in rats after acute vocal fold injury [ 31 , 32 ]. Interestingly, treatment with antioxidants prevented age-associated changes in rat vocal folds [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…We used the rabbit as in vivo model given the similarities to human vocal fold anatomy and biology [ 34 , 35 ]. Furthermore, the rabbit is a well-validated model in studies focused on the vocal folds [ 29 , 30 , 36 – 45 ]. Water volume restriction was chosen as the systemic dehydration method to mimic a more physiologically-realistic state that can be better translated to human behavior [ 46 – 48 ].…”

Section: Introductionmentioning

confidence: 99%

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Proteomic analysis reveals that aging rabbit vocal folds are more vulnerable to changes caused by systemic dehydration

Nascimento¹,

Bailey²,

Santos³

et al. 2022

BMC Genomics

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Background Older adults are more prone to develop systemic dehydration. Systemic dehydration has implications for vocal fold biology by affecting gene and protein expression. The objective of this study was to quantify vocal fold protein changes between two age groups and hydration status, and to investigate the interaction of age and hydration status on protein expression, which has not been investigated in the context of vocal folds before. Comparative proteomics was used to analyze the vocal fold proteome of 6.5-month-old and > 3-year-old rabbits subjected to water ad libitum or water volume restriction protocol. Results Young and older adult rabbits (n = 22) were either euhydrated (water ad libitum) or dehydrated by water volume restriction. Dehydration was confirmed by body weight loss of − 5.4% and − 4.6% in young and older groups, respectively, and a 1.7-fold increase of kidney renin gene expression in the young rabbits. LC-MS/MS identified 2286 proteins in the rabbit vocal folds of young and older adult rabbits combined. Of these, 177, 169, and 81 proteins were significantly (p ≤ 0.05) affected by age, hydration status, or the interaction of both factors, respectively. Analysis of the interaction effect revealed 32 proteins with opposite change patterns after dehydration between older and young rabbit vocal folds, while 31 proteins were differentially regulated only in the older adult rabbits and ten only in the young rabbits in response to systemic dehydration. The magnitude of changes for either up or downregulated proteins was higher in the older rabbits. These proteins are predominantly related to structural components of the extracellular matrix and muscle layer, suggesting a disturbance in the viscoelastic properties of aging vocal fold tissue, especially when subjected to systemic dehydration. Conclusions Water restriction is a laboratory protocol to assess systemic dehydration-related changes in the vocal fold tissue that is translatable to human subjects. Our findings showed a higher number of proteins differentially regulated with a greater magnitude of change in the vocal folds of older adult rabbits in the presence of systemic dehydration compared to younger rabbits. The association of these proteins with vocal fold structure and biomechanical properties suggests that older human subjects may be more vulnerable to the effects of systemic dehydration on vocal function. The clinical implications of these protein changes warrant more investigation, but age should be taken into consideration when evaluating vocal treatment recommendations that interfere with body fluid balance.

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Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Proteomic analysis reveals that aging rabbit vocal folds are more vulnerable to changes caused by systemic dehydration

Nascimento¹,

Bailey²,

Santos³

et al. 2022

BMC Genomics

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“…Global changes in the laryngeal proteome in response to external factors have not been studied at length. Only a handful of studies have addressed changes in the laryngeal proteome as they relate to cigarette smoke exposure, 20 senescent muscle, 21 systemic dehydration, 22 decellularization, 23 and cancer. 24 , 25 , 26 , 27 , 28 , 29 However, in a literature search on laryngeal proteomics following IL, the only entries were two previous studies from our group.…”

Section: Discussionmentioning

confidence: 99%

Larynx proteomics after jellyfish collagen IL: Increased ECM/collagen and suppressed inflammation

Bowen

Ekbom

Hunter

et al. 2022

Laryngoscope Investig Oto

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Objectives/Hypothesis Compare proteomic profiles of rabbit vocal folds (VFs) injected with micronized cross‐linked jellyfish collagen “collagen Type 0” (MX‐JC) against two clinical products for injection medialization laryngoplasty (IL). Study Design Animal model. Methods Left recurrent laryngeal nerve sectioning and IL were performed in New Zealand White rabbits ( N = 6/group). Group 1 received (MX‐JC) and adipose‐derived stem cells (ADSCs), Group 2, MX‐JC alone; Group 3, cross‐linked hyaluronic acid; and Group 4, micronized acellular dermis. Animals were sacrificed at 4 and 12 weeks. Proteomic profiling of injected versus noninjected VFs by nano‐liquid chromatography, tandem mass spectrometry, and reactome gene ontology analysis was performed. Results Overall, 37–61 proteins were found to be upregulated and 60–284 downregulated in injected versus non‐injected VFs (>1.5 fold, false discovery rate‐adjusted p < .05). Over‐representation analysis (% of total) revealed top up‐regulated pathways at 4 and 12 weeks, respectively: Group 1, keratan sulfate metabolism (46%) and cellular processes (29%); Group 2, extracellular matrix (ECM)/collagen processes (33%) and beta oxidation (39%); Group 3, cellular processes (50%) and energy metabolism (100%); and Group 4, keratan sulfate metabolism (31%) and inflammation (50%). Top downregulated pathways were: Group 1, Inflammation (36%) and glucose/citric acid metabolism (42%); Group 2, cell signaling (38%) and glucose/citric acid metabolism (35%); Group 3, keratan sulfate metabolism (31%) and ECM/collagen processes (48%); and Group 4, glucose/citric acid metabolism (33%) and ECM/collagen processes (43%). Conclusions MX‐JC “collagen Type 0” upregulates pathways related to ECM/collagen formation and downregulates pathways related to inflammation suggesting that it is promising biomaterial for IL. Level of Evidence NA

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Impact of Rehydration Following Systemic Dehydration on Vocal Fold Gene Expression

et al. 2023

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ObjectiveBiological data on the beneficial effects of vocal fold rehydration are lacking. This study aimed to examine the effects of acute systemic dehydration on vocal fold gene expression and determine whether rehydration would reverse these changes.MethodsMale New Zealand White rabbits (N = 24, n = 8/group) provided the animal model. Systemic dehydration was induced by 5 days of water volume restriction. Rehydration was provided by ad‐lib water for 3 days following dehydration. Euhydrated rabbits were used as the control group. Vocal fold tissue was dissected. Seventeen genes were selected based on physiological function and role in supporting vocal fold structure, oxidative stress, hemodynamics, and extracellular matrix turnover. Relative gene expression was assessed by RT‐qPCR.ResultsRehydration following systemic dehydration can modulate gene expression, with expression patterns suggesting that rehydration reverses dehydration‐induced changes in over half of the tested genes. CLIC5 (chloride intracellular channel 5) and EFEMP1 (EGF containing fibulin extracellular matrix protein 1) genes were significantly upregulated in the dehydration group compared with the euhydrated control. A1BG (alpha‐1B‐glycoprotein) and IL1RAP (interleukin 1 receptor accessory protein) were downregulated by rehydration compared with the dehydration group.ConclusionThis study provides molecular evidence for a transcriptional response to rehydration following acute systemic dehydration in the vocal folds. These data are the first to study gene expression following realistic dehydration and rehydration paradigms and provide biological data to support clinical recommendations to increase water intake after acute dehydration.Level of EvidenceN/A Laryngoscope, 2023

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Furosemide-induced systemic dehydration alters the proteome of rabbit vocal folds

Cited by 7 publications

References 98 publications

Proteomic analysis reveals that aging rabbit vocal folds are more vulnerable to changes caused by systemic dehydration

Proteomic analysis reveals that aging rabbit vocal folds are more vulnerable to changes caused by systemic dehydration

Larynx proteomics after jellyfish collagen IL: Increased ECM/collagen and suppressed inflammation

Impact of Rehydration Following Systemic Dehydration on Vocal Fold Gene Expression

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