Whole transcriptome analysis of smoker palatal mucosa identifies multiple downregulated innate immunity genes

Wang, Yun; Anderson, Eric P.; Tatakis, Dimitris N.

doi:10.1002/jper.19-0467

Cited by 11 publications

(9 citation statements)

References 51 publications

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“…The significantly higher expression of IL33 in healing gingiva and its strong association with miRNA suggest that IL33 may also play a significant regulatory role in oral wound healing. In a recent report from this laboratory, IL33 expression levels in palatal gingiva was strongly negatively associated with cotinine levels and smokers’ gingiva expressed significantly lower IL33 levels than non‐smokers under homeostatic conditions 24 . This finding, along with the results of the present study, raises the possibility that IL‐33 could emerge as a possible target for improvement of impaired healing in smokers.…”

Section: Discussionsupporting

confidence: 77%

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Integrative mRNA/miRNA expression analysis in healing human gingiva

Wang

Tatakis

2020

Journal of Periodontology

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Background MicroRNAs (miRNAs) are implicated in the epigenetic regulation of complex biological processes. Their possible role in human oral wound healing, a process that differs from cutaneous wound healing by being faster and typically scar‐free, has been unexplored. This report presents the miRNA expression profile of experimental human oral wounds and an integrative analysis of mRNA/miRNA expression. Methods Nine healthy volunteers provided standardized normal and 5‐day healing palatal biopsies, used for next generation miRNA and mRNA sequencing analysis, correlation and network analysis, real‐time PCR (qPCR) and immunohistochemistry. Results On average, 169 significantly regulated precursor miRNAs were detected, including 21 novel miRNAs, selectively confirmed by PCR. Hsa‐miR‐223‐3p and hsa‐miR‐124‐3p were, respectively, the most up‐ and downregulated miRNAs in healing gingiva. Hsa‐miR‐124‐3p had the most predicted mRNA target interactions, with angiogenesis‐related genes the most enriched. Correlation analysis showed the highest correlation between hsa‐miR‐181a‐3p and SERPINB1; hsa‐miR‐223‐5p and SLC2A3; hsa‐miR‐1301 and MS4A7. In addition, SERPINB1 mRNA had the most associations with differentially regulated miRNAs. IL33 was the only cytokine significantly correlated with miRNAs (ρ > 0.95). qPCR and immunohistochemistry verified the significant upregulation of SERPINB1 and IL33 in healing gingiva. Conclusions This study is the first to report on the miRNome of healing human gingiva and to provide an integrative analysis of miRNA/mRNA expression during human oral wound healing; the results offer novel insights into the participating molecular mechanisms and raise the possibility of SERPINB1 and IL‐33 as potential wound healing therapeutic targets.

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Section: Discussionsupporting

confidence: 77%

“…Fixed biopsy samples were processed as previously detailed 24 . Slides were stained with primary antibody against SERPINB1 and IL‐33 and followed by a horseradish peroxidase detection system and development in 3,3′‐diaminobenzidine.…”

Section: Methodsmentioning

confidence: 99%

Integrative mRNA/miRNA expression analysis in healing human gingiva

Wang

Tatakis

2020

Journal of Periodontology

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“…Inclusion criteria were: aged 21 to 38 years (age limits based on evidence of delayed wound healing in older adults 28 ); no coagulation disorders or other systemic disease; no medications affecting periodontal status in the previous 6 months; no allergy to study medications or materials; no pregnancy/lactation/contraceptive medication; no tobacco or marijuana use (non‐smoker status verified by exhaled air carbon monoxide as previously described 29 ); full‐mouth plaque score 30 and full‐mouth bleeding score ≤ 20% at study entry; adequate anteroposterior arch length for required wound size and spacing; able to easily tolerate maxillary impression making and use of palatal template; no contraindication to receiving PHT, other study medications (anesthetics, analgesics), or gingival surgery. Study exclusion criteria were: untreated caries; inadequate endodontic therapy or tooth mobility > 1 on maxillary teeth; untreated periodontitis; previous surgery on the palate.…”

Section: Methodsmentioning

confidence: 99%

Topical phenytoin effects on palatal wound healing

Doshi

McAuley

Tatakis

2020

Journal of Periodontology

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Background: The clinical benefits of autogenous soft tissue grafts are countered by donor site morbidity. The aim of this prospective split-mouth clinical trial is to assess clinical, histological and patient outcomes following topical phenytoin (PHT) treatment of experimental palatal wounds. Methods: Systemically healthy adults were recruited. One 6 mm diameter wound (posterior) and one 4 mm diameter wound (anterior), each 1-1.5 mm deep, were created on both sides of the palate. Wounds on one randomly chosen side received 10% phenytoin USP and contralateral wounds received carrier alone. Biopsies were harvested from anterior wounds (Day 1 or Day 5) and were routinely processed for histology. Posterior wounds were left undisturbed to clinically evaluate healing (using photographs and Healing Score Index) on Days 1, 5, 14, and 21. Questionnaires were used to assess patient-centered outcomes. Data analysis was performed using generalized logistic and generalized linear mixed models. Results: Twenty participants completed all visits. 30% of participants reported more pain on control side than the PHT side at Day 1 (P = 0.014). PHT treated sites were more likely to not exhibit swelling (OR = 9.35; P = 0.009) and to not experience pain on palpation (OR = 6.278; P = 0.007). PHT significantly and timedependently affected granulation tissue appearance (P = 0.004). Histologically, there were no significant differences between control and PHT, at any time point (P ≥ 0.853). Conclusions: The results of the present study, the first one to report on topical PHT as palatal wound treatment, suggest that PHT application on palatal wounds could result in improved healing outcomes. K E Y W O R D S biopsy, gingiva, phenytoin, wound healing 1 INTRODUCTION The available evidence indicates that autogenous soft tissue grafts are the most predictable and most stable long-term option for both root coverage. 1,2 and gingival augmentation. 3,4 However, autogenous soft tissue graft harvesting is accompanied by postoperative morbidity associated with the resulting palatal wounds, which leads to poorer patient experiences, at least in the short term. 5-8 Because of the morbidity and complications associated with autogenous soft tissue graft donor sites, several clinical studies have tested various post-operative protocols, such as application of hemostatic agents, 9 collagen matrix, 10 ozonated oil, 11 platelet concentrates, 12,13

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“…In a follow‐up study, the same group found that smokers express 830 contrasting genes compared with nonsmokers. These differentially expressed genes were associated with innate immunity and antimicrobial response and were downregulated in smokers 103 …”

Section: Palatal Soft Tissue Wound Healingmentioning

confidence: 99%

“…These differentially expressed genes were associated with innate immunity and antimicrobial response and were downregulated in smokers. 103…”

Section: Genes Implicated In Palatal Soft-tissue Wound Healingmentioning

confidence: 99%

Wound healing dynamics, morbidity, and complications of palatal soft‐tissue harvesting

Tavelli

Barootchi

Stefanini

et al. 2022

Periodontology 2000

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Palatal‐tissue harvesting is a routinely performed procedure in periodontal and peri‐implant plastic surgery. Over the years, several surgical approaches have been attempted with the aim of obtaining autogenous soft‐tissue grafts while minimizing patient morbidity, which is considered the most common drawback of palatal harvesting. At the same time, treatment errors during the procedure may increase not only postoperative discomfort or pain but also the risk of developing other complications, such as injury to the greater palatine artery, prolonged bleeding, wound/flap sloughing, necrosis, infection, and inadequate graft size or quality. This chapter described treatment errors and complications of palatal harvesting techniques, together with approaches for reducing patient morbidity and accelerating donor site wound healing. The role of biologic agents, photobiomodulation therapy, local and systemic factors, and genes implicated in palatal wound healing are also discussed.

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Whole transcriptome analysis of smoker palatal mucosa identifies multiple downregulated innate immunity genes

Cited by 11 publications

References 51 publications

Integrative mRNA/miRNA expression analysis in healing human gingiva

Integrative mRNA/miRNA expression analysis in healing human gingiva

Topical phenytoin effects on palatal wound healing

Wound healing dynamics, morbidity, and complications of palatal soft‐tissue harvesting

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