Macrophage Depletion Impairs Skeletal Muscle Regeneration: the Roles of Pro-fibrotic Factors, Inflammation, and Oxidative Stress

Inflammation ◽  
2016 ◽  
Vol 39 (6) ◽  
pp. 2016-2028 ◽  
Author(s):  
Weihua Xiao ◽  
Yu Liu ◽  
Peijie Chen
PLoS ONE ◽  
2016 ◽  
Vol 11 (8) ◽  
pp. e0159411 ◽  
Author(s):  
Keith G. Avin ◽  
Neal X. Chen ◽  
Jason M. Organ ◽  
Chad Zarse ◽  
Kalisha O’Neill ◽  
...  

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Xiaoguang Liu ◽  
Weihua Xiao ◽  
Lifang Zhen ◽  
Yongzhan Zhou ◽  
Jian Shou

Objective Skeletal muscle contusion is one of the most common muscle injury in sports medicine and traumatology. Bone marrow mesenchymal stem cells (BMSCs) transplantation is a promising strategy for muscle regeneration. However, the roles of BMSCs, especially the mechanisms involved, in the regeneration of contused skeletal muscle are still not fully recognized. The aim of the study is to evaluate the potential of BMSCs transplantation for muscle regeneration and mechanisms involved after contusion. Methods Ninety-nine C57BL/6J mice were divided into three groups: control group (n=11), muscle contusion and BMSCs treated group (n=44), muscle contusion and sham treated group (n=44). BMSCs were immediately transplanted into gastrocnemius muscles (GMs) following direct contusion. At different time points (3, 6, 12 and 24 days) post-injury, the animals were killed and then GMs were harvested. Morphological and gene expression analyses were used to elevate the effect of BMSCs transplantation and mechanisms involved. Results The results indicate that BMSCs transplantation impairs muscle regeneration, as well as more fibrotic scar formation after skeletal muscle contusion. Furthermore, macrophages, inflammatory cytokines, chemokines, matrix metalloproteinases and oxidative stress related enzymes were significantly increased after BMSCs transplantation. These results suggest that BMSCs transplantation impairs skeletal muscle regeneration and that macrophages, inflammatory cytokines, chemokines, matrix metalloproteinases and oxidative stress related enzymes may be involved in the process. Conclusions BMSCs transplantation aggravates inflammation, oxidative stress and fibrosis, and impairs skeletal muscle regeneration, which shed new light on the role of BMSCs in regenerative medicine and cautions the application of BMSCs for muscle injury.


2019 ◽  
Vol 10 ◽  
Author(s):  
Xiaoguang Liu ◽  
Lifang Zheng ◽  
Yongzhan Zhou ◽  
Yingjie Chen ◽  
Peijie Chen ◽  
...  

2007 ◽  
Vol 282 (43) ◽  
pp. 31453-31459 ◽  
Author(s):  
Germana Zaccagnini ◽  
Fabio Martelli ◽  
Alessandra Magenta ◽  
Chiara Cencioni ◽  
Pasquale Fasanaro ◽  
...  

2017 ◽  
Vol 41 (3) ◽  
pp. 228-238 ◽  
Author(s):  
Xiaoguang Liu ◽  
Yu Liu ◽  
Linlin Zhao ◽  
Zhigang Zeng ◽  
Weihua Xiao ◽  
...  

2021 ◽  
Vol 22 (11) ◽  
pp. 5491
Author(s):  
Yuya Takahashi ◽  
Tatsunori Shimizu ◽  
Shunsuke Kato ◽  
Mitsuhiko Nara ◽  
Yumi Suganuma ◽  
...  

Superoxide dismutase (SOD) is a major antioxidant enzyme for superoxide removal, and cytoplasmic SOD (SOD1) is expressed as a predominant isoform in all cells. We previously reported that renal SOD1 deficiency accelerates the progression of diabetic nephropathy (DN) via increasing renal oxidative stress. To evaluate whether the degree of SOD1 expression determines regeneration capacity and sarcopenic phenotypes of skeletal muscles under incipient and advanced DN conditions, we investigated the alterations of SOD1 expression, oxidative stress marker, inflammation, fibrosis, and regeneration capacity in cardiotoxin (CTX)-injured tibialis anterior (TA) muscles of two Akita diabetic mouse models with different susceptibility to DN, DN-resistant C57BL/6-Ins2Akita and DN-prone KK/Ta-Ins2Akita mice. Here, we report that KK/Ta-Ins2Akita mice, but not C57BL/6-Ins2Akita mice, exhibit delayed muscle regeneration after CTX injection, as demonstrated by the finding indicating significantly smaller average cross-sectional areas of regenerating TA muscle myofibers relative to KK/Ta-wild-type mice. Furthermore, we observed markedly reduced SOD1 expression in CTX-injected TA muscles of KK/Ta-Ins2Akita mice, but not C57BL/6-Ins2Akita mice, along with increased inflammatory cell infiltration, prominent fibrosis and superoxide overproduction. Our study provides the first evidence that SOD1 reduction and the following superoxide overproduction delay skeletal muscle regeneration through induction of overt inflammation and fibrosis in a mouse model of progressive DN.


Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 758
Author(s):  
Eun Bee Choi ◽  
Jae Hun Jeong ◽  
Hye Min Jang ◽  
Yu Jeong Ahn ◽  
Kyu Hyeon Kim ◽  
...  

Obesity and insulin resistance accelerate aging-related sarcopenia, which is associated with iron load and oxidative stress. Lipocalin-2 (LCN2) is an iron-binding protein that has been associated with skeletal muscle regeneration, but details regarding its role in obese sarcopenia remain unclear. Here, we report that elevated LCN2 levels in skeletal muscle are linked to muscle atrophy-related inflammation and oxidative stress in leptin-deficient ob/ob mice. RNA sequencing analyses indicated the LCN2 gene expression is enhanced in skeletal muscle of ob/ob mice with sarcopenia. In addition to muscular iron accumulation in ob/ob mice, expressions of iron homeostasis-related divalent metal transporter 1, ferritin, and hepcidin proteins were increased in ob/ob mice compared to lean littermates, whereas expressions of transferrin receptor and ferroportin were reduced. Collectively, these findings demonstrate that LCN2 functions as a potent proinflammatory factor in skeletal muscle in response to obesity-related sarcopenia and is thus a therapeutic candidate target for sarcopenia treatment.


2019 ◽  
Vol 10 ◽  
Author(s):  
Xiaoguang Liu ◽  
Lifang Zheng ◽  
Yongzhan Zhou ◽  
Yingjie Chen ◽  
Peijie Chen ◽  
...  

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