Integrative mRNA/miRNA expression analysis in healing human gingiva

Abstract

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.

Complement factor D as a predictor of Achilles tendon healing and long‐term patient outcomes

“…SERPINB1 was also detected as another novel biomarker involved in effective tendon repair and regeneration. Our findings of increased SERPINB1 expression at 2‐weeks post‐injury are in line with previous observations of higher SERPINB1 expression both at the mRNA and protein levels during the early proliferative phase in healing gingiva 38 …”

“…Our findings of increased SERPINB1 expression at 2-weeks post-injury are in line with previous observations of higher SERPINB1 expression both at the mRNA and protein levels during the early proliferative phase in healing gingiva. 38 These observations also confirm SERPINB1 synthesis and function at the site of injury. However, our observation that lower SERPINB1 levels at 2-weeks' postinjury were associated with better outcome suggests that this time point represents a transitional phase from the inflammatory-into the proliferative-phase of healing.…”

“…To elucidate novel proteomic profiles of ATR healing and its relation to clinical outcome, 35 patients (9 females) with acute ATR were assembled of which 16 (3 females) exhibited good outcomes, and 19 (6 females) with poor outcomes were collected with median age 37 (32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42) years and body mass index (BMI) 25.4 (24.1-28.1) kg/m 2 (Table 1). All the clinical data were validated, collected, and shown in Table 1.…”

miRNA‐encapsulated abiotic materials and biovectors for cutaneous and oral wound healing: Biogenesis, mechanisms, and delivery nanocarriers

“…Figure 3a represents the miRNA expression profile through the initial wound healing in human gingiva, indicating the variation in miRNA expression profile in wound healing gingiva compared with normal gingiva. 127 In addition, specific miRNAs are suggested to have the potential to ameliorate the oral wound healing process. The positive effect of miRNA‐21 in palatal wound healing has been evaluated on a mice model.…”

“…The colors of this heatmap exhibit the upregulation and downregulation with green and red, respectively. Reproduced from Reference 127 with permission from Wiley. (b) The expression of miR‐150, miR‐200b, miR‐223, miR‐144, miR‐379, and miR‐222 in three samples of inflamed and noninflamed gingiva using real‐time PCR (* p < 0.01).…”