副教授 - 林怡彣

牙周病與系統性疾病之相關性

Porphyromonas gingivalis (P. gingivalis) 是一種導致牙周組織破壞的格蘭氏陰性絕對厭氧桿狀菌。在本實驗室先前之研究指出，除了LPS、fimbriae、gingipains外，由P. gingivalis 所分泌之GroEL蛋白亦為其重要之致病因子，GroEL可藉由活化NF-κb路徑而促使牙周韌帶細胞促骨吸收相關細胞因子IL-6和IL-8的分泌；GroEL亦可藉由活化牙周韌帶細胞RANKL及抑制ALP之分泌而促進破骨作用；在動物實驗中，將P. gingivalis之GroEL接種到大鼠牙齦後顯著增加牙周組織之炎症反應和齒槽骨骨質的流失，以上結果明確指出GroEL確實亦為P. gingivalis之重要毒力因子之一，對於牙周炎病人而言其為重要的潛在免疫抗原(potential immunedominant antigen)。目前認為牙周致病菌或其發炎因子能夠藉由兩種方式進入人體，第一為經由腸胃道的系統，研究指出牙周炎確實會影響到腸胃道菌相的呈現，此外，其亦會經由血液循環進入全身的器官進而與系統性疾病的生成相關。近年來，陸續有許多流行病學的文獻指出牙周病確實與系統性疾病間具有一定的相關性，這些疾病包含了心血管疾病、癌症、呼吸道感染性疾病、流產，糖尿病，甚至是阿茲海默症等等都與之息息相關。本實驗室先前之研究結果指出P. gingivalis 之GroEL蛋白會藉由促進血管新生作用而導致腫瘤之加速生長，此外GroEL蛋白與其他系統性疾病包括主動脈瘤(AAA; abdominal aortic aneurysms)(圖一)、敗血症(Sepsis) (圖二)、移植後血管病變(CAV; cardiac allograft vasculopathy)…等等則為本實驗室目前之研究重點。

期刊論文（*通訊作者，＃共同作者）

1. Tseng HT, Lin YW, Huang CY, Shih CM, Tsai YT, Liu CW, Tsai CS and Lin FY. Animal Models for Heart Transplantation Focusing on the Pathological Conditions. Biomedicines. 2023;11.

2. Sung SY, Lin YW, Wu CC, Lin CY, Hsu PS, Periasamy S, Nagarajan B, Hsieh DJ, Tsai YT, Tsai CS and Lin FY. Supercritical carbon dioxide-decellularized arteries exhibit physiologic-like vessel regeneration following xenotransplantation in rats. Biomater Sci. 2023;11:2566-2580.

3. Lin FY, Tsai YT, Huang CY, Lai ZH, Tsai CS, Shih CM, Lin CY and Lin YW*. GroEL of Porphyromonas gingivalis-induced microRNAs accelerate tumor neovascularization by downregulating thrombomodulin expression in endothelial progenitor cells. Mol Oral Microbiol. 2023. (責任作者)

4. Hsu CY, Huang CY, Shih CM, Lin YW, Huang PH, Lin SJ, Liu CW, Lin CY and Lin FY. Tumor Necrosis Factor Superfamily 14 (LIGHT) Restricts Neovascularization by Decreasing Circulating Endothelial Progenitor Cells and Function. Int J Mol Sci. 2023;24.

5. Lin YW^†, Tsai CS^†, Huang CY, Tsai YT, Shih CM, Lin SJ, Li CY, Lin CY, Sung SY and Lin FY. Far-Infrared Therapy Decreases Orthotopic Allograft Transplantation Vasculopathy. Biomedicines. 2022;10:1089. (共同第一作者)

6. Tseng HT, Wu XC, Huang CY, Shih CM, Lin YW* and Lin FY*. The Impact of SARS-CoV-2 Infection, and Application of Immunosuppressive Agents in Kidney Transplant Recipients Suffering from COVID-19. Pharmaceuticals (Basel). 2021;14. (共同責任作者)

7. Tsai CS, Lin FY, Liu YC, Lin YW, Tsai YT, Huang CY, Lin SJ, Li CY, Lin CY, Tseng HT and Shih CM. Transferring Plasmon Effect on a Biological System: Expression of Biological Polymers in Chronic Rejection and Inflammatory Rat Model. Polymers (Basel). 2021;13.

8. Lin HH, Lin YW, Wu CY, Hsiao FP, Lai YL and Hung SL. Stimulatory effects of Porphyromonas gingivalis GroEL protein on interleukin-6 and interleukin-8 in human osteoblasts. J Formos Med Assoc. 2021;120:150-156.

9. Lin FY, Lin YW, Shih CM, Lin SJ, Tung YT, Li CY, Chen YH, Lin CY, Tsai YT and Huang CY. A Novel Relative High-Density Lipoprotein Index to Predict the Structural Changes in High-Density Lipoprotein and Its Ability to Inhibit Endothelial-Mesenchymal Transition. Int J Mol Sci. 2021;22.

10. Chan WH, Huang NC, Lin YW, Lin FY, Tsai CS and Yeh CC. Intrathecal IGF2 siRNA injection provides long-lasting anti-allodynic effect in a spared nerve injury rat model of neuropathic pain. PloS one. 2021;16:e0260887.

11. Lin FY, Shih CM, Huang CY, Tsai YT, Loh SH, Li CY, Lin CY, Lin YW* and Tsai CS*. Dipeptidyl Peptidase-4 Inhibitor Decreases Allograft Vasculopathy Via Regulating the Functions of Endothelial Progenitor Cells in Normoglycemic Rats. Cardiovasc Drugs Ther. 2020. (共同責任作者)

12. Tsai YT, Lin FY, Lin CS, Loh SH, Li CY, Lin CY, Lin YW* and Tsai CS*. B-type natriuretic peptide enhances fibrotic effects via matrix metalloproteinase-2 expression in the mouse atrium in vivo and in human atrial myofibroblasts in vitro. Transl Res. 2019;208:30-46. (共同責任作者)

13. Shih CM, Lin FY, Yeh JS, Lin YW, Loh SH, Tsao NW, Nakagami H, Morishita R, Sawamura T, Li CY, Lin CY and Huang CY. Dysfunctional high density lipoprotein failed to rescue the function of oxidized low density lipoprotein-treated endothelial progenitor cells: a novel index for the prediction of HDL functionality. Transl Res. 2019;205:17-32.

14. Chen YC, Lin FY, Lin YW, Cheng SM, Lin RH, Chuang CL, Sheu JS, Chen SM, Chang CC and Tsai CS. DAPT Plus Cilostazol is Better Than Traditional DAPT or Aspirin Plus Ticagrelor as Elective PCI for Intermediate-to-Highly Complex Cases: Prospective, Randomized, PRU-Based Study in Taiwan. Am J Cardiovasc Drugs. 2019;19:75-86.

15. Chen YC, Lin FY, Lin YW, Cheng SM, Chang CC, Lin RH, Chuang CL, Sheu JS, Chen SM and Tsai CS. Platelet MicroRNA 365-3p Expression Correlates with High On-treatment Platelet Reactivity in Coronary Artery Disease Patients. Cardiovasc Drugs Ther. 2019;33:129-137.

16. Lin YW^#, Huang CY^#, Shih CM, Tsai YT, Lin CS, Lin CY, Li CY, Loh SH, Lin CY, Lin FY and Tsai CS. Eotaxin-2 induces monocytic apoptosis in patients who have undergone coronary artery bypass surgery and in THP-1 cells in vitro regulated by thrombomodulin. Am J Transl Res. 2018;10:3133-3149. (共同第一作者)

17. Pai CC, Lin YW, Tsai YT, Loh SH, Lin CY, Lin CS, Lin YC, Ke HY, Lin FY and Tsai CS. A Thrombomodulin Gene Polymorphism (C1418T) Is Associated with Early Outcomes in Patients Undergoing Coronary Artery Bypass Graft Surgery with a Conventional Cardiopulmonary Bypass during Hospitalization. Medicines (Basel). 2017;4.

18. Lu HY, Huang CY, Shih CM, Lin YW, Tsai CS, Lin FY and Shih CC. A potential contribution of dipeptidyl peptidase-4 by the mediation of monocyte differentiation in the development and progression of abdominal aortic aneurysms. J Vasc Surg. 2017;66:1217-1226 e1.