Nature Communications (Nov 2023)
FNIP1 abrogation promotes functional revascularization of ischemic skeletal muscle by driving macrophage recruitment
- Zongchao Sun,
- Likun Yang,
- Abdukahar Kiram,
- Jing Yang,
- Zhuangzhuang Yang,
- Liwei Xiao,
- Yujing Yin,
- Jing Liu,
- Yan Mao,
- Danxia Zhou,
- Hao Yu,
- Zheng Zhou,
- Dengqiu Xu,
- Yuhuan Jia,
- Chenyun Ding,
- Qiqi Guo,
- Hongwei Wang,
- Yan Li,
- Li Wang,
- Tingting Fu,
- Shijun Hu,
- Zhenji Gan
Affiliations
- Zongchao Sun
- State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing University
- Likun Yang
- State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing University
- Abdukahar Kiram
- State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing University
- Jing Yang
- State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing University
- Zhuangzhuang Yang
- Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Suzhou Medical College, Soochow University
- Liwei Xiao
- State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing University
- Yujing Yin
- State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing University
- Jing Liu
- State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing University
- Yan Mao
- State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing University
- Danxia Zhou
- State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing University
- Hao Yu
- State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing University
- Zheng Zhou
- State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing University
- Dengqiu Xu
- State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing University
- Yuhuan Jia
- State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing University
- Chenyun Ding
- State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing University
- Qiqi Guo
- State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing University
- Hongwei Wang
- Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University
- Yan Li
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University
- Li Wang
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University
- Tingting Fu
- State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing University
- Shijun Hu
- Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Suzhou Medical College, Soochow University
- Zhenji Gan
- State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing University
- DOI
- https://doi.org/10.1038/s41467-023-42690-9
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 18
Abstract
Abstract Ischaemia of the heart and limbs attributable to compromised blood supply is a major cause of mortality and morbidity. The mechanisms of functional angiogenesis remain poorly understood, however. Here we show that FNIP1 plays a critical role in controlling skeletal muscle functional angiogenesis, a process pivotal for muscle revascularization during ischemia. Muscle FNIP1 expression is down-regulated by exercise. Genetic overexpression of FNIP1 in myofiber causes limited angiogenesis in mice, whereas its myofiber-specific ablation markedly promotes the formation of functional blood vessels. Interestingly, the increased muscle angiogenesis is independent of AMPK but due to enhanced macrophage recruitment in FNIP1-depleted muscles. Mechanistically, myofiber FNIP1 deficiency induces PGC-1α to activate chemokine gene transcription, thereby driving macrophage recruitment and muscle angiogenesis program. Furthermore, in a mouse hindlimb ischemia model of peripheral artery disease, the loss of myofiber FNIP1 significantly improved the recovery of blood flow. Thus, these results reveal a pivotal role of FNIP1 as a negative regulator of functional angiogenesis in muscle, offering insight into potential therapeutic strategies for ischemic diseases.
