2. Academic Validation
  3. Sulforaphane modulates macrophage polarization via JAK1/STAT1 inhibition to promote tendon repair in tendinopathy

Sulforaphane modulates macrophage polarization via JAK1/STAT1 inhibition to promote tendon repair in tendinopathy

  • Int Immunopharmacol. 2025 Aug 4:163:115302. doi: 10.1016/j.intimp.2025.115302.
Wang Zhang 1,  Xue Fang 2,  Yuping Liu 3,  Changhuan Liu 4,  Can Yao 5,  Jiahui Guo 6,  Peilong Wu 7,  Wei Tan 8,  Lekai Zhu 9,  Wei Gao 10,  Zheng Wang 11,  Xin Wang 12
Affiliations

Affiliations

  • 1 Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Elderly Hip Fracture Diagnosis and Treatment Center, Zhongnan Hospital of Wuhan University, Wuhan 430071, China. Electronic address: 2023283030152@whu.edu.cn.
  • 2 Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Elderly Hip Fracture Diagnosis and Treatment Center, Zhongnan Hospital of Wuhan University, Wuhan 430071, China. Electronic address: 2022283030094@whu.edu.cn.
  • 3 Department of anesthesiology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610066, China. Electronic address: 2856804540@qq.com.
  • 4 Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Elderly Hip Fracture Diagnosis and Treatment Center, Zhongnan Hospital of Wuhan University, Wuhan 430071, China. Electronic address: 2024283030162@whu.edu.cn.
  • 5 Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan 430071, China. Electronic address: 2023305233088@whu.edu.cn.
  • 6 Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan 430071, China. Electronic address: 2023305233098@whu.edu.cn.
  • 7 Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan 430071, China. Electronic address: 2023305233111@whu.edu.cn.
  • 8 Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China. Electronic address: 2428631967@qq.com.
  • 9 Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Elderly Hip Fracture Diagnosis and Treatment Center, Zhongnan Hospital of Wuhan University, Wuhan 430071, China. Electronic address: 2050144456@qq.com.
  • 10 Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan 430071, China. Electronic address: znyycg@126.com.
  • 11 Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Elderly Hip Fracture Diagnosis and Treatment Center, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Clinical Medical Research Center of Trauma and Microsurgery, Wuhan 430071, China. Electronic address: wangzhengemail@whu.edu.cn.
  • 12 Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Elderly Hip Fracture Diagnosis and Treatment Center, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Clinical Medical Research Center of Trauma and Microsurgery, Wuhan 430071, China. Electronic address: wangxinznyy@whu.edu.cn.
PMID: 40763479 DOI: 10.1016/j.intimp.2025.115302
Abstract

Background: Imbalanced M1/M2 macrophage polarization is central to tendinopathy pathogenesis. Sulforaphane (SFN), a natural compound with anti-inflammatory properties, may modulate macrophage polarization.

Methods: This study utilized a collagenase-induced mouse model of tendinopathy to evaluate the therapeutic effects of local SFN administration on tendinopathy in vivo. Furthermore, the effects of SFN on macrophage polarization were investigated in vitro, and RNA Sequencing was used to explore the mechanisms by which SFN regulates macrophage polarization in vivo. Finally, an ex vivo human pathological tendon culture system was employed to explore the therapeutic effects of SFN on tendinopathic lesions.

Results: In this study, we found that SFN modulated the polarization of M1 macrophages towards M2 macrophages, thereby effectively modulating the inflammatory response. RNA Sequencing and Western blot analyses indicated that the effect of SFN was mediated through the JAK1/STAT1 signaling pathway. In a collagenase-induced mouse model of tendinopathy, local injection of SFN led to a significant improvement in tendon tissue structure, with the Collagen matrix restoring its natural dense parallel arrangement. Furthermore, there was an increase in local M2 macrophages and a decrease in M1 macrophages, which promoted the resolution of inflammation. Finally, the immunomodulatory effect of SFN on macrophages was also validated in tendon tissue from patients with tendinopathy.

Conclusions: SFN can effectively alleviate tendinopathy by promoting the polarization of M1 macrophages towards M2 macrophages, an effect achieved through the inhibition of the JAK1/STAT1 signaling pathway, thereby providing a promising therapeutic approach for the treatment of tendinopathy.

Keywords

Inflammation; JAK/STAT signaling pathway; Macrophage polarization; Sulforaphane; Tendinopathy.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z