Signal transduction and biological function of tuft cells / 中华微生物学和免疫学杂志

Tuft cells are highly specialized epithelial cells with distinct transcriptional profiles and biological functions. Recent studies have revealed that tuft cells are widely existed in a range of tissues, including digestive system, respiratory system and periodontal tissues, playing essential roles in mediating host-microbial interaction and initiating type Ⅱ immune response. Although tuft cells share many commons regarding their morphological characteristics and expression profiles, emerging evidence indicates that tuft cells possess a certain degree of heterogeneity in different tissues or loci. Of note, tuft cells consistently express a variety of taste receptors and their downstream signal transduction machineries to detect and respond a wide range of chemicals in the microenvironment or bacterial metabolites. This review discussed the molecular basis of taste signal transduction and biological functions of tuft cells in different tissues.

Regulation effect of lipopolysaccharide on the alternative splicing and function of sweet taste receptor T1R2 / 华西口腔医学杂志

OBJECTIVES@#To identify the alternative splicing isoform of mouse sweet taste receptor T1R2, and investigate the effect of lipopolysaccharide (LPS) local injection on T1R2 alternative splicing and the function of sweet taste receptor as one of the bacterial virulence factors.@*METHODS@#After mouse taste bud tissue isolation was conducted, RNA extraction and reverse transcription polymerase chain reaction (PCR) were performed to identify the splicing isoform of T1R2. Heterologous expression experiments @*RESULTS@#T1R2 splicing isoform T1R2_Δe3p formed sweet taste receptors with T1R3, which could not be activated by sweet taste stimuli and significantly downregulated the function of canonical T1R2/T1R3. Local LPS injection significantly increased the expression ratio of T1R2_Δe3p in mouse taste buds.@*CONCLUSIONS@#LPS stimulation affects the alternative splicing of mouse sweet taste receptor T1R2 and significantly upregulates the expression of non-functional isoform T1R2_Δe3p, suggesting that T1R2 alternative splicing regulation may be one of the mechanisms by which microbial infection affects host taste perception.

Presence of carbohydrate binding modules in extracellular region of class C G-protein coupled receptors (C GPCR): An in silico investigation on sweet taste receptor

Sweet taste receptor (STR) is a C GPCR family member and a suggested drug target for metabolic disorders such asdiabetes. Detailed characteristics of the molecule as well as its ligand interactions mode are yet considerably unclear due toexperimental study limitations of transmembrane proteins. An in silico study was designed to find the putative carbohydratebinding sites on STR. To this end, a-D-glucose and its a-1,4-oligomers (degree of polymerization up to 14) were chosen asprobes and docked into an ensemble of different conformations of the extracellular region of STR monomers (T1R2 andT1R3), using AutoDock Vina. Ensembles had been sampled from an MD simulation experiment. Best poses were furtherenergy-minimized in the presence of water molecules with Amber14 forcefield. For each monomer, four distinct bindingregions consisting of one or two binding pockets could be distinguished. These regions were further investigated withregard to hydrophobicity and hydrophilicity of the residues, as well as residue compositions and non-covalent interactionswith ligands. Popular binding regions showed similar characteristics to carbohydrate binding modules (CBM). Observationof several conserved or semi-conserved residues in these binding regions suggests a possibility to extrapolate the results toother C GPCR family members. In conclusion, presence of CBM in STR and, by extrapolation, in other C GPCR familymembers is suggested, similar to previously proposed sites in gut fungal C GPCRs, through transcriptome analyses. STRmodes of interaction with carbohydrates are also discussed and characteristics of non-covalent interactions in C GPCRfamily are highlighted.

Effect of Astragalus Polysaccharide on Sweet Taste Receptor Pathway in Intestine of Rat Model Induced by High-sugar and High-fat Diet / 中国实验方剂学杂志

Objective:To observe the effect of astragalus polysaccharide (APS) on taste receptor 1 member 2 (T1R2)/taste receptor 1 member 3 (T1R3) sweet taste receptor pathway in intestine of rat model induced by high-sugar and high-fat diet. Method:SD rats were randomly divided into normal group, high-sugar and high-fat group and astragalus polysaccharide group. Rats in high-sugar and high-fat group and astragalus polysaccharide groups were fed with high-sugar and high-fat diet for 16 weeks, while rats in astragalus polysaccharide group were fed with APS (0.7 g·kg-1, per day) for 8 weeks during this period. Serum samples were collected to determine the levels of fasting blood glucose, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Intestinum tenue was collected to determine mRNA expressions of T1R2/T1R3, α-gustducin (Gα gust), transient receptor potential cation channel subfamily member 5 (TRPM5) and proglucagon (PG) gene by Real-time PCR, and protein expressions of T1R2, Gα gust and glucagon-like peptide-1 (GLP-1) protein by Western blot. Result:Rats in high-sugar and high-fat group had significantly higher levels of TC, TG and LDL-C, and lower HDL-C level in serum than those in normal group (Pα gust and PG genes in intestine, were significantly down-regulated in high-sugar and high-fat group (PPα gust, TRPM5 and PG genes in intestine were significantly up-regulated in astragalus polysaccharide group (Pα gust and GLP-1 protein expressions was consistent with that of T1R2, Gα gust and GLP-1 mRNA expressions. Protein expressions of T1R2, Gα gust and GLP-1 and mRNA expression of T1R3 were significantly lower in astragalus polysaccharide group than those of control group (PConclusion:APS could improve disturbance of lipid metabolism and impairment of intestinal sweet taste receptor pathway for rat model induced by high-sugar and high-fat diet.

An Expression Levels Analysis of the Bitter Taste Receptors in the Murine Exocrine Glands

Recent findings indicate that Type 2 taste receptors (T2Rs) are expressed outside the gustatory system, including in the gastrointestinal tracts and the exocrine glands, such as the submandibular (SM), parotid (P), lacrimal (L) glands and pancreas (PC). Specifically, T2Rs are found in some of the gastrointestinal endocrine cells, and these cells secreted peptide hormones in response to stimulation by bitter-tasting compounds. The results show that T2Rs may have significant physiological roles besides bitter taste reception. The functions of the T2Rs in the exocrine glands remain poorly understood. An expression levels analysis of T2Rs will help to determine those functions in the exocrine glands. The expression levels of the T2Rs in the exocrine glands were discovered via the qPCR. C57BL/6J mice of 42~60-day-old were used. Messenger RNAs were extracted from S, P, L and PC. Cloned DNAs were synthesized by reverse transcription. Quantitative PCRs were performed using the SYBR Green method. The expression levels of the T2Rs were calculated as relative expression levels to that of the GAPDH. The statistical significance among the observed exocrine glands was tested using the variance analysis (ANOVA test). Tas2r108, out of murine 35 T2Rs, was the most highly expressed in every observed exocrine gland. This finding was similar to previous results from tongue papillae, but the expression levels were lower than those of the tongue papillae. Tas2r137 of SM, P, L and PC were expressed a little lower than that of tongue papillae. The T2Rs in the exocrine glands may play slightly different roles from those in the tongue. We suggest that physiological studies such as a patch clamp and functional Ca²⁺ imaging of acinar cells are necessary for understanding the Tas2r108 functions.

Limonin inhibits the PM2.5 inhalation-induced airway inflammation and mucus hypersecretion in rats / 基础医学与临床

Objective To investigate the inhibitory effect of limonin on airway inflammation and mucus hypersecre-tion. Methods The experiment was divided into three groups(n=10),namely blank control group,PM2.5 group (the rat models of chronic airway inflammation were established by aerosolized PM2.5 suspension) and PM2.5+limonin group(intervening with the extract from tangerine peel). mRNA,protein of inflammatory cytokines,mucin (MUC) and TAS2Rs were measured by ELISA,RT-PCR and Western blot respectively. Results The mRNA and protein expression of IL-1β, CINC-1 and MUC5AC and MUC5B in PM2.5 group were significantly higher than those in control group(P<0.05),and the expression of MUC5AC protein in broncho alveolar lavage fluid(BALF) was increased. Compared with PM2.5 stimulated group,mRNA and protein of TAS2R14 in PM2.5+limonin inter-vented group were significantly higher (P<0.05). Moreover, the expression of IL-1β, CINC-1 and MUC5AC, MUC5B was lower than PM2.5 group (P<0.05).While the expression of MUC5B was mainly increased in BALF.Conclusions The production of mucin can be inhibited by aerosolized limonin, meanwhile the secretion of mucin also can be promoted.This effect is achieved by activating the expression of TAS2Rs in the lungs, which enhances the anti-inflammatory effect of airway inflammation.

Effects of denatonium benzoate on calcium binding protein S100A9 and mucus in the airways of asthmatic mice / 医学研究生学报

number of goblet cells, mucus secretion and mucin MUC5AC content in lung tissues. Results S100A9 in BALF of group B was (11.89±0.77) ng/mL, S100A9 integrated optical density (IOD) value in airway epithelial cells was 13.96±1.62, PAS stain area /epithelial cell area was (12.53±1.21)%, relative value of MUC5AC / NADPH was 173.91±4.29, all of the above were higher than those of group A [(6.19±0.61) ng/mL, 4.97±0.30, (1.94±0.18)%, 1];S100A9 levels, IOD of S100A9 in airway epithelial cells, PAS stain area / epithelial cell area (%), relative value of MUC5AC / NADPH in group C [(10.69±0.79) ng / ml, 11.80±0.72, (10.61±0.61)%, 94.65±1.59], group D[(9.49±0.99) ng/mL, 10.39±0.59, (8.63±0.62)%, 82.08±1.12], group E [(7.54± 0.42) ng/mL, 5.63±0.84, (4.59±0.87)%, 26.30±1.94] were lower than group B, which showed a dose-dependent reduction and the difference was statistically significant (P<0.05 or P<0.01). Conclusion DB downregulates the expression level of Ca2+-binding protein S100A9 and the mucus secretion amount of the airway goblet cells in rats.

Containment effects of bitter taste native ingredient from traditional Chinese medicine on airway inflammation process via bitter taste receptor pathway / 中国免疫学杂志

Objective:To investigate the anti-inflammatory effects of bitter taste receptor (TAS2Rs) in the treatment of chronic airway inflammation by bitter Chinese medicine.Methods: The experiment was divided into three groups (n=8),namely blank control group,PM2.5 group (the rat models of chronic airway inflammation were established by aerosolized PM2.5 suspension) and PM2.5+limonin group (intervening with the extract from Tangerine peel).The expression of mRNA and protein of inflammatory cytokines and TAS2Rs in bronchial/pulmonary tissue were detected by ELISA,RT-PCR and Western blot respectively.Results: The mRNA and protein expression levels of TNF-α and IL-13 in PM2.5 stimulated group were significantly higher than those in control group,while the TAS2R14 were not significantly changed.The mRNA and protein expression levels of TNF-α and IL-13 in the limonin intervention group was lower than that in the PM2.5 group,and the TAS2R14 were significantly increased.Conclusion: The production and release of inflammatory cytokines in the chronic inflammatory airway can be curbed by inhaling the components of bitter Chinese herbal medicine.And then,the TAS2Rs in the lungs can be activated by the bitter components to increase its expression.Therefore,it is considered that bitter Chinese herbal medicine to play the airway anti-inflammatory effect is achieved through the activation of the airway TAS2Rs.

Taste signal transduction and the role of taste receptors in the regulation of microbial infection / 华西口腔医学杂志

Taste receptors guide individuals to consume nutrients while avoiding potentially noxious substances. Interestingly, recent studies have shown that taste receptors are also expressed beyond the taste buds, including brain, respiratory system, and digestive system, etc. These extragustatory taste receptors play important roles in microbial infection, nutrient uptake and host homeostasis. Mang extragustatory taste receptors have been proposed to sense microorganisms and regulate host innate defense. More importantly, polymorphisms of genes encoding taste receptor, particularly bitter taste receptor, are linked to different innate defensive responses. This review introduces the molecular basis of taste signal transduction, and the role of taste receptors in the regulation of innate immunity during microbial infection were further discussed in detail.

Effect of denatonium benzoate on airway inflammation and remodeling in asthmatic mice / 重庆医学

Objective To evaluate the effect of denatonium benzoaten on α-smooth muscle actin (α-SMA),subepithelial collagen and airway inflammation in asthmu mice.Methods Forty-five BALB/c mice were divided into 3 groups,normal control group (A group),asthma model group (B group),asthma model+ denatonium benzoaten group(C group);α-SMA detected by using immunohistochemistry,lung sections were stained with Masson to detect subepithelial collagen,HE stain method was used to observe the airway inflammation the images were analyzed with semi-quantitative computer.Results The deposition of α-SMA、subepithelial collagen and inflammation degree in C group was significantly reduced compared with B group,the difference were statistically significant(P＜0.05).Conclusion Denatonium benzoaten can improve airway remodeling in asthmatic mice.

Establishment and application of screening model for anti-asthmatic natural active ingredients based on bitter taste receptors in lung tissue / 中草药

Objective: To construct high-throughput screening cell model targeting TAS2R14 receptor and lay the foundation for the search of effective, novel natural anti-asthma drugs with low toxicity. Methods: The pLVX-AcGFP1-N1-TAS2R14 lentivirus vector carrying green fluorescent protein (GFP) was constructed. The lentiviral vector was transfected into HEK HEK293T cells, collected high titer lentiviral concentration liquid and infected HEK293T cells, established cell model highly specific expressed TAS2R14 receptor gene. The TAS2R14 cell model was used to screen 120 kinds of Chinese herb extracts and chemical monomers. Results: The calculated Z' values of the cell model were 0.69 and 0.66, and Citri Reticulatae Pericarpium extract and its efficacy material limonin, Ginkgo Semen extract and its efficacy material rutin and quinine agitated TAS2R14 cell model. Conclusion: The constructed TAS2R14 cell model is stable and sensitive for screening anti-asthma drugs, and three kinds of Chinese materia medica monomers have the potential agonist the activity on TAS2R14 receptor.

Seleção de aptâmeros que se ligam ao receptor humano para o gosto doce / Screening for aptamers that bind to the human sweet taste receptor (hT1R2/hT1R3)

Foi demonstrado que o gosto doce é transduzido por receptores acoplados a proteína G classe III (GPCRs), T1R2 e T1R3. Essas proteínas exibem longas extremidades amino-terminais que formam um domínio de ligação globular extracelular. Elas são expressas em células associadas ao gosto (células epiteliais que constituem os botões gustativos nas papilas gustativas), que respondem a moléculas associadas ao gosto doce. Quando T1R2 e T1R3 são co-expressas em células heterólogas, elas respondem, como heterômeros, a uma série de açúcares, alguns D-aminoácidos, edulcorantes artificiais e proteínas doces. Foi também demonstrado que o receptor humano T1R2/T1R3 para o gosto doce apresenta múltiplos sítios de ligação. Para melhor compreender a estrutura desse receptor e responder à pergunta de como um único quimiorreceptor pode ser responsivo a uma variedade de ligantes, foi utilizada a abordagem denominada evolução sistemática de ligantes por enriquecimento exponencial (SELEX) para isolar, a partir de uma biblioteca combinatória de oligonucleotídeos, aptâmeros de RNA resistentes a nuclease que se ligam ao receptor humano para o gosto doce com alta afinidade. Após um enriquecimento de doze ciclos do pool original de RNA contendo em torno de 1013 sequências diferentes (contra preparações de membrana de células HEK293T que expressam hT1R2/hT1R3) e outros ciclos de contrasseleção negativa (para eliminar moléculas de RNA que se ligam de forma inespecífica à membrana de nitrocelulose e a outras proteínas diferentes do alvo, ou seja, proteínas de membrana de células HEK293T selvagem), realizou-se a transcrição reversa do RNA seguida de amplificação por PCR e sequenciamento. Aptâmeros do ciclo 12 com sequências consenso foram selecionados, e a ligação de alguns deles com hT1R2/hT1R3 foi então avaliada. Cinco desses aptâmeros mostram claramente uma maior afinidade por células HEK293T que expressam hT1R2/hT1R3. Como segunda parte desta tese, estudamos outro receptor, denominado CD36, que, como o receptor T1R2/T1R3, é expresso na língua. Estudos indicam que ele age como receptor gustativo de gordura. Neste trabalho, verificamos que essa proteína é expressa em uma subpopulação de neurônios olfatórios presentes no epitélio olfatório, indicando que ela pode ter também uma função olfatória, ainda não caracterizada

It has been shown that sweet taste is transduced by the Class III G Protein-Coupled Receptors (GPCRs) T1R2 and T1R3, which show long N-termini that form a globular extracellular ligand-binding domain. These receptors are expressed in the taste cells (epithelial cells that constitute the taste buds in taste papillae) that respond to sweet tastants, and when T1R2 and T1R3 are coexpressed in heterologous cells, they respond, as heteromers, to a series of sugars, some D-amino acids, artificial sweeteners and sweet proteins. It has also been demonstrated that the sweet taste receptor has multiple binding sites. In order to better understand the structure of this receptor and answer the question of how a single chemoreceptor can respond to a variety of ligands, we used the combinatorial oligonucleotide library screening approach, denominated Systematic Evolution of Ligands by Exponential Enrichment (SELEX), to isolate nuclease-resistant RNA aptamers that bind to the human sweet taste receptor with high affinity. Following a twelve round enrichment of the previous random RNA pool containing around 1013 different sequences (against membrane preparations of hT1R2/hT1R3-expressing HEK293T cells) and negative counterselection cycles (to eliminate RNA molecules that bind nonspecifically to the nitrocellulose membrane and to proteins other than the target, that is, HEK293T cells membrane proteins), the RNA was reverse-transcribed for DNA sequencing. Aptamers from cycle 12 with consensus sequences were selected, and the binding of some of them to the human sweet taste receptor was then evaluated. Five out of the aptamers clearly show greater affinity for hT1R2/hT1R3-expressing HEK293T cells than for hT1R2/hT1R3-non-expressing HEK293T cells. In this thesis we have also analyzed another receptor, denominated CD36, which is also expressed in the tongue. Studies indicate that it acts as a receptor for fat. In this work, we found that CD36 is expressed in a subset of the olfactory neurons localized in the olfactory epithelium, indicating that it may also have an as yet uncharacterized olfactory function

Sweet Taste-Sensing Receptors Expressed in Pancreatic beta-Cells: Sweet Molecules Act as Biased Agonists

The sweet taste receptors present in the taste buds are heterodimers comprised of T1R2 and T1R3. This receptor is also expressed in pancreatic beta-cells. When the expression of receptor subunits is determined in beta-cells by quantitative reverse transcription polymerase chain reaction, the mRNA expression level of T1R2 is extremely low compared to that of T1R3. In fact, the expression of T1R2 is undetectable at the protein level. Furthermore, knockdown of T1R2 does not affect the effect of sweet molecules, whereas knockdown of T1R3 markedly attenuates the effect of sweet molecules. Consequently, a homodimer of T1R3 functions as a receptor sensing sweet molecules in beta-cells, which we designate as sweet taste-sensing receptors (STSRs). Various sweet molecules activate STSR in beta-cells and augment insulin secretion. With regard to intracellular signals, sweet molecules act on STSRs and increase cytoplasmic Ca2+ and/or cyclic AMP (cAMP). Specifically, when an STSR is stimulated by one of four different sweet molecules (sucralose, acesulfame potassium, sodium saccharin, or glycyrrhizin), distinct signaling pathways are activated. Patterns of changes in cytoplasmic Ca2+ and/or cAMP induced by these sweet molecules are all different from each other. Hence, sweet molecules activate STSRs by acting as biased agonists.

Expression of Bitter Taste Receptors in Human Nasal Respiratory Epithelium

The nasal cavity encounters various irritants during inhalation such as dust and pathogens. To detect and remove these irritants, it has been postulated that the nasal mucosa epithelium has a specialized sensing system. The oral cavity, on the other hand, is known to have bitter taste receptors (T2Rs) that can detect harmful substances to prevent ingestion. Recently, solitary chemosensory cells expressing T2R subtypes have been found in the respiratory epithelium of rodents. In addition, T2Rs have been identified in the human airway epithelia. However, it is not clear which T2Rs are expressed in the human nasal mucosa epithelium and whether they mediate the removal of foreign materials through increased cilia movement. In our current study, we show that human T2R receptors indeed function also in the nasal mucosa epithelium. Our RT-PCR data indicate that the T2R subtypes (T2R3, T2R4, T2R5, T2R10, T2R13, T2R14, T2R39, T2R43, T2R44, T2R 45, T2R46, T2R47, T2R48, T2R49, and T2R50) are expressed in human nasal mucosa. Furthermore, we have found that T2R receptor activators such as bitter chemicals augments the ciliary beating frequency. Our results thus demonstrate that T2Rs are likely to function in the cleanup of inhaled dust and pathogens by increasing ciliary movement. This would suggest that T2Rs are feasible molecular targets for the development of novel treatment strategies for nasal infection and inflammation.

The Role of the Sweet Taste Receptor in Enteroendocrine Cells and Pancreatic beta-Cells

The sweet taste receptor is expressed in taste cells located in taste buds of the tongue. This receptor senses sweet substances in the oral cavity, activates taste cells, and transmits the taste signals to adjacent neurons. The sweet taste receptor is a heterodimer of two G protein-coupled receptors, T1R2 and T1R3. Recent studies have shown that this receptor is also expressed in the extragustatory system, including the gastrointestinal tract, pancreatic beta-cells, and glucose-responsive neurons in the brain. In the intestine, the sweet taste receptor regulates secretion of incretin hormones and glucose uptake from the lumen. In beta-cells, activation of the sweet taste receptor leads to stimulation of insulin secretion. Collectively, the sweet taste receptor plays an important role in recognition and metabolism of energy sources in the body.

Stimulation of Glucagon Like Peptide-1 Secretion in Enteroendocrine L cells / 당뇨병

GLP-1 (glucagon like peptide-1) is new anti-diabetic drug with a number of beneficial effects. It stimulates glucose dependant insulin secretion and restoration of beta cell mass through enhancement of islet mass. However, it is easily inactivated after being secreted from enteroendocrine L cells. Recent trial to increased GLP-1 is to directly stimulate L cells through its receptor located in the surface of L cell. Taste receptor in the apical surface of L cell is activated by various tastants contained in the food. Tongue perceives taste sense through the heterotrimeric G-protein (alpha-gustducin) and its downstream signaling cascades. Same taste receptors are also expressed in enteroendocrine cells. In duodenal L cell, alpha-gustducin was detected by immunofluorescence stainig at the luminal projections of enteroendocrine cells. And several other taste signaling elements were also found in L cells. Ingestion of sweet or bitter compounds revealed stimulation of GLP-1 secretion and the regulation of plasma insulin and glucose. In this review, I will briefly introduce the possibilities to stimulate GLP-1 secretion though the membrane receptor in enteroendocrine cell. And it will be the good candidate to develop the treatment modality for obesity, diabetes and abnormal gut motility.

Change of taste preference and taste bud after unilateral lingual nerve transection in rat

PURPOSE OF STUDY: Lingual nerve damage can be caused by surgery or trauma such as physical irriatation, radiation, chemotherapy, infection and viral infection. Once nerve damage occurred, patients sometimes complain taste change and loss of taste along with serious disturbance of tongue. The purpose of this study was to evaluate the effects of unilateral lingual nerve transection on taste as well as on the maintenance of taste buds. MATERIALS AND METHODS: Male Sprague-Dawley rats weighing 220-250g received unilateral transection of lingual nerve, subjected to the preference test for various taste solutions (0.1M NaCl, 0.1M sucrose, 0.01M QHCl, or 0.01M HCl) with two bottle test paradigm at 2, 4, 6, or 8 weeks after the operation. Tongue was fixed with 8% paraformaldehyde. After fixation, they were observed with scanning electron microscope(JSM-840A(R), JEOL, JAPAN) and counted the number of the dorsal surface of the fungiform papilla for changes of fungiform papilla. And, Fungiform papilla were obtained from coronal sections of the anterior tongue(cryosection). After cryosection, immunostaining with Galpha gust(I-20)(Santa Cruz Biotechnology, USA), PLCbeta2(Q-15)(Santa Cruz Biotechnology, USA), and T1R1(Alpha Diagnostic International, USA) were done. Immunofluorescence of labeled taste bud cells was examined by confocal microscopy(F92-300., Olympus, JAPAN). RESULTS: The preference score for salty and sweet tended to be higher in the operated rats with statistical significance, compared to the sham rats. Fungiform papilla counting were decreased after lingual nerve transaction. In 2 weeks, maximum differences occurred. Gustducin and T1R1 expressions of taste receptor in 2 and 4 weeks were decreased. PLCbeta2 were not expressed in both experimental and control group. CONCLUSION: This study demonstrated that the taste recognition for sweet and salty taste changed by week 2 and 4 after unilateral lingual nerve transection. However, regeneration related taste was occurred in the presence of preserving mesoneurial tissue and the time was 6 weeks. Our results demonstrated that unilateral lingual nerve damage caused morphological and numerical change of fungiform papilla. It should be noted in our study that lingual nerve transection resulted in not only morphological and numerical change but also functional change of fungiform papillae.