Establishment and Development:

Liu Ping Research Lab has a good foundation in the research of peripheral vascular tissue lesions, atherosclerosis and vascular remodeling. The project leader has been engaged in basic and clinical research of vascular remodeling for many years, especially in the research of peripheral vascular membrane, identifying promising novel targeted therapies for treating atherosclerosis and vascular remodeling. Transcription factors are key controllers of gene expression. We have investigated whether Smad, mitogen-activated protein kinase (MAPK), and integrin signaling pathways cross-talk to enhance adventitial fibroblast (AF) bioactivity, which was activated by transforming growth factor (TGF)-beta1 and inhibited by Gax. Our findings indicate that cross-talk among Smad, MAPK, and integrin signaling pathways may account mainly for the mechanism of AF functions. Gax is a promising therapeutic gene for dissecting the signaling pathways controlling AF bioactivities. With a small but dedicated team, we set out to establish a research laboratory that would be recognized for its excellence and impact. Since its inception, our lab has gone through a remarkable journey of growth and development. We have also identified that adventitial inflammation induces vascular remodeling via the interactions of multiple inflammatory cytokines and local Gax gene transfer in vivo can significantly inhibit these interactions and thereby attenuate local inflammation and vascular remodeling. Additionally, we have forged valuable collaborations and partnerships with Jiwei Cui and Fengming Liu, et.al to further enhance our research capabilities.

Team Members:

Our team is composed of Principal Investigator (PI), Research Director, Project Coordinator or Research Associate, Research Assistant and a number of students affiliated to Shandong University, Qilu Medical College. Together, they work tirelessly to their objectives and research areas as below.

Research Areas:

1. Gax gene interferes with chemerin mediated perivascular adipocyte proliferation and differentiation (81170274). National Natural Science Foundation Project 2012-2015.

2. Study on the mechanism of MEOX2 signaling axis targeting mediated by perivascular preadipocyte derived exosomes to regulate perivascular fibroblast function and vascular remodeling. National Natural Science Foundation Project 2022-2025

3. The role of gap connexin 43 in the onset and progression of ventricular fibrillation (30871039). National Natural Science Foundation Project 2009-2011.

4. Effect of Gax gene on the proliferation of perivascular adipocytes (2009ZRB019BS). Shandong Province Nature Fund Project

5. Study on the mechanism of FSP1 regulation of vascular outer membrane fibroblast function mediated by mutual dialogue between RAGE, Wnt and STAT signaling pathways (2015GSF121008). Key Research and Development Program of Shandong Province

6. Study on the synergistic targeting of LncRNA UCA1 and miR-373 to regulate PI3K-Akt-mTOR-Stat3 signaling pathway mediating the function of vascular outer membrane fibroblasts (GG201703080074). Shandong Province Nature Fund Project

7. Study on the mechanism of vascular remodeling mediated by GXYLT2-AP-Notch signaling axle-mediated dialogue between perivascular adipocytes and extravascular fibroblasts (ZR2020MH041). Shandong Province Nature Fund Project

8. Study on the mechanism of Copb1/miR-721/Gax/PHF20L1 signaling axis targeted by exosomes to regulate perivascular adipocytes and vascular remodeling. Jinan Science and Technology Bureau, 2021-2024

9. Clinical study on the role of midsection atrial natriuretic peptide precursor (MR-proANP) in diagnosis and prediction of heart failure (201602153). Jinan Science and Technology Bureau, Under research

10. Study on the mechanism of MEOX2 signaling axis targeting peripheral vascular tissue cells and vascular remodeling. Shenzhen Science and Technology Innovation Commission, In research.

Research Achievements:

With regard to basic research, our team leader has been engaged in mechanisms of vascular remodeling for many years, especially in the study of the vascular adventitia. The main work includes: (1) Revealing for the positive and negative regulators of vascular adventitial fibroblasts (AF) affecting vascular remodeling first time: The study found that the interaction of three signaling pathways - Smad, MAPK, and Integrin - determines the biological activity of AF. TGF-β1 enhances interactions among these pathways, eventually influencing the function of AF; however, specific growth inhibition homologous genes (Gax) inhibit pathways described as before. This study was published as the cover story in ATVB, the prestigious journal of the American College of Cardiology (AHA) (2008 SCI Impact Factor 7.4) [Liu P, et al. ATVB,2008, 28:725-731.] (2) The inhibitory effect of Gax gene overexpression on proliferative vascular remodeling in the vascular adventitia was reported for the first time: This team applied adenovirus carrying Gax to locally transfect the vascular adventitia in vivo, and found that Ad-Gax transfection could inhibit the proliferation and migration of vascular cells, induce vascular cell apoptosis and reduce the expression of inflammatory factors. Ad-Gax transfection significantly reduced the thickness of the vascular wall at the lesion site and inhibited negative vascular remodeling in vivo. The study has been published in Atherosclerosis, the leading European journal [Liu P, et al. Atherosclerosis, 2010;212(2):398-405.]

Main Publications:

1. Wang J, Tan JS, Hua L, Sheng Q, Huang X, Liu P. Genetic predisposition of both waist circumference and hip circumference increased the risk of venous thromboembolism [published online ahead of print, 2022 Nov 16]. ThrombHaemost. 2022;10.1055/a-1980-8852. doi:10.1055/a-1980-8852.

2. Wang J, Huang X, Fu C, Sheng Q, Liu P. Association between triglyceride glucose index, coronary artery calcification and multivessel coronary disease in Chinese patients with acute coronary syndrome. Cardiovasc Diabetol. 2022 Sep 16;21(1):187.

3. Huang X, Fu C, Liu W, Liang Y, Li P, Liu Z, Sheng Q, Liu P. Chemerin-induced angiogenesis and adipogenesis in 3 T3-L1 preadipocytes is mediated by lncRNA Meg3 through regulating Dickkopf-3 by sponging miR-217. Toxicol Appl Pharmacol. 2019;385:114815.

4. Cai Hua Fu, MD, Ping Liu,MD,PhD, Pei Lun Li,MD,Wen Hui Liu,MD. FSP1 promotes the biofunctions of adventitial fibroblast through the crosstalk among RAGE, JAK2/STAT3 and Wnt3a/β-catenin signaling pathways. J Cell Mol Med. 2019;23(11):7246-7260.

5. Jiang Y, Liu P, Jiao W, Meng J, Feng J. Gax suppresses chemerin/CMKLR1-induced preadipocyte biofunctions through the inhibition of Akt/mTOR and ERK signaling pathways. J Cell Physiol. 2018;233(1):572-586.

6. Liu P, Jiang Y, Meng J. Relationship between serum uric acid, metabolic syndrome and resting heart rate in Chinese elderly. Obes Res Clin Pract. 2016;10(2):159-168.

7. Liu P, Kong F, Wang J, Lu Q, Xu H, Qi T, Meng J. Involvement of IGF-1 and MEOX2 in PI3K/Akt1/2 and ERK1/2 pathways mediated proliferation and differentiation of perivascular adipocytes. Exp Cell Res. 2015;331(1):82-96.

8. Liu P, Feng J, Kong F, Lu Q, Xu H, Meng J, Jiang Y. Gax inhibits perivascular preadipocyte biofunction mediated by IGF-1 induced FAK/Pyk2 and ERK2 cooperative pathways. Cell Signal. 2014;26(12):3036-3045.

9. Liu P, Zhang C, Zhao YX, Feng JB, Liu CX, Chen WQ, Yao GH, Zhang M, Wang XL, Zhang Y. Gax gene transfer inhibits vascular remodeling induced by adventitial inflammation in rabbits. Atherosclerosis. 2010;212(2):398-405.

10. Liu P, Zhang C, Feng JB, Zhao YX, Wang XP, Yang JM, Zhang MX, Wang XL, Zhang Y. Cross talk among Smad, MAPK, and integrin signaling pathways enhances adventitial fibroblast functions activated by transforming growth factor-beta1 and inhibited by Gax. ArteriosclerThrombVasc Biol. 2008;28(4):725-731.

Facilities & Resources:

Our state-of-the-art facilities and cutting-edge technology enable us to conduct research that is both rigorous and innovative. Our medical experimental center includes molecular biology experiment platform, cell biology experiment platform, immunology and histopathology experiment platform, microscopic characterization platform, electrophysiology platform, SPF experimental animal platform, evidence-based medicine platform, biomedical sample bank, etc. Covering an area of more than 6,000 square meters, it has basic and high-end instruments and equipment for the study of the structure and function of biological macromolecules, cell morphology and function, the construction and experiment of animal models, and the storage, processing and analysis of clinical samples, with a total value of more than 73.15 million yuan, including 13 equipment with more than 1 million yuan. Including the sorting high-end flow cytometry analyzer, Beckman high-end flow cytometry, laser scanning confocal microscopy, multispectral scanning microscopy, laser microdissection, IVIS Spectrum CT small animal live optical imaging system, digital PCR, cell energy metabolism system, 2D image-guided biological irradiation system, mouse magnetic resonance body fat detector, pyrophosphate sequence analyzer, confocal microRaman spectrometer, automatic single-cell transcription analyzer and digital pathological section scanne, etc.

Collaborations & Partnerships:

We believe in the power of collaboration. That's why we have forged partnerships with our partners to further advance our research.

Recreational Activities:

In the Teachers’ Day, we were all happy to send warm thoughts of love and regards to our loving teachers. We've drawn inspiration from Ping Liu, a professor of Cardiology at Shandong University who grew interested in doing more to connect students with their passions and creative energies.

“We need to be cranking out innovators, problem solvers, and creative thinkers, people that aren't afraid to take risks, people that don't want to just regurgitate answers, and people that are finding their passions in life.” He said once.

Other Features:

1. Expectation of breakthrough solutions

   Our lab pursues disruptive innovations and are called to “imagine the impossible” (LIL). Rather than settling for incremental improvements, our mission is typically to deliver “breakthrough solutions” and create places “where today’s moonshots become tomorrow’s breakthroughs”.

2. Targeted collaboration

   While labs’ typically impose a problem focus, we draw on collaborative technologies and dynamics to generate solutions. iLabs, for example, claims that it is based on “cross-sector collaborations that bring people together,” and eLab “focuses on collaborative innovation.” This approach presumes that all participants, regardless of institutional power differences, should treat one another as equal partners.

3. Focus on experimentation

   Labs like to stress that they “create space for experimentation through facilitated processes”. We encourage team partners to “try things out on a small scale, take risks, prototype, test and accept failure as part of progress”, re-inventing their own methods and approaches as they go along.

Contact:

For more information or inquiries, please contact us:

Team assistant:: shuaiyongzhang139@163.com

Lab PI: lping@sdu.edu.cn or cardiac@163.com