scholarly journals Reduction of Superoxide Dismutase 1 Delays Regeneration of Cardiotoxin-Injured Skeletal Muscle in KK/Ta-Ins2Akita Mice with Progressive Diabetic Nephropathy

2021 ◽  
Vol 22 (11) ◽  
pp. 5491
Author(s):  
Yuya Takahashi ◽  
Tatsunori Shimizu ◽  
Shunsuke Kato ◽  
Mitsuhiko Nara ◽  
Yumi Suganuma ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Superoxide Dismutase ◽  
Diabetic Nephropathy ◽  
Muscle Regeneration ◽  
Diabetic Mouse ◽  
Skeletal Muscle Regeneration ◽  
Oxidative Stress Marker ◽  
Regeneration Capacity ◽  
Cross Sectional

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.

scholarly journals Skeletal Muscle Regeneration and Oxidative Stress Are Altered in Chronic Kidney Disease

PLoS ONE ◽  
2016 ◽  
Vol 11 (8) ◽  
pp. e0159411 ◽  
Author(s):  
Keith G. Avin ◽  
Neal X. Chen ◽  
Jason M. Organ ◽  
Chad Zarse ◽  
Kalisha O’Neill ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Muscle Regeneration ◽  
Skeletal Muscle Regeneration ◽  
And Oxidative Stress

scholarly journals PL-003 BMSCs transplantation aggravate inflammation, oxidative stress, fibrosis and impair skeletal muscle regeneration

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Xiaoguang Liu ◽  
Weihua Xiao ◽  
Lifang Zhen ◽  
Yongzhan Zhou ◽  
Jian Shou
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Matrix Metalloproteinases ◽  
Inflammatory Cytokines ◽  
Muscle Regeneration ◽  
Muscle Injury ◽  
Treated Group ◽  
Skeletal Muscle Regeneration ◽  
Skeletal Muscle Contusion ◽  
And Oxidative Stress

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.

scholarly journals Corrigendum: BMSC Transplantation Aggravates Inflammation, Oxidative Stress, and Fibrosis and Impairs Skeletal Muscle Regeneration

2019 ◽  
Vol 10 ◽  
Author(s):  
Xiaoguang Liu ◽  
Lifang Zheng ◽  
Yongzhan Zhou ◽  
Yingjie Chen ◽  
Peijie Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Skeletal Muscle Regeneration

scholarly journals p66ShcAand Oxidative Stress Modulate Myogenic Differentiation and Skeletal Muscle Regeneration after Hind Limb Ischemia

2007 ◽  
Vol 282 (43) ◽  
pp. 31453-31459 ◽  
Author(s):  
Germana Zaccagnini ◽  
Fabio Martelli ◽  
Alessandra Magenta ◽  
Chiara Cencioni ◽  
Pasquale Fasanaro ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Hind Limb ◽  
Myogenic Differentiation ◽  
Limb Ischemia ◽  
Skeletal Muscle Regeneration ◽  
Hind Limb Ischemia

scholarly journals Tissue specific muscle extracellular matrix hydrogel improves skeletal muscle regeneration in vivo over non-matched tissue source

2020 ◽  
Author(s):  
Jessica L. Ungerleider ◽  
Monika Dzieciatkowska ◽  
Kirk C. Hansen ◽  
Karen L. Christman
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Extracellular Matrix ◽  
Regenerative Medicine ◽  
Expression Analysis ◽  
Muscle Regeneration ◽  
Gene Expression Analysis ◽  
Skeletal Muscle Regeneration ◽  
Cross Sectional ◽  
Tissue Specific

AbstractDecellularized extracellular matrix (ECM) hydrogels present a novel, clinical intervention for a myriad of regenerative medicine applications. The source of ECM is typically the same tissue to which the treatment is applied; however, the need for tissue specific ECM sources has not been rigorously studied. We hypothesized that tissue specific ECM would improve regeneration through preferentially stimulating physiologically relevant processes (e.g. progenitor cell proliferation and differentiation). One of two decellularized hydrogels (tissue specific skeletal muscle or non mesoderm-derived lung) or saline were injected intramuscularly two days after notexin injection in mice (n=7 per time point) and muscle was harvested at days 5 and 14 for histological and gene expression analysis. Both injectable hydrogels were decellularized using the same detergent and were controlled for donor characteristics (i.e. species, age). At day 5, the skeletal muscle ECM hydrogel significantly increased the density of Pax7+ satellite cells in the muscle. Gene expression analysis at day 5 showed that skeletal muscle ECM hydrogels increased expression of genes implicated in muscle contractility. By day 14, skeletal muscle ECM hydrogels improved muscle regeneration over saline and lung ECM hydrogels as shown through a shift in fiber cross sectional area distribution towards larger fibers. This data indicates a potential role for muscle-specific regenerative capacity of decellularized, injectable muscle hydrogels. Further transcriptomic analysis of whole muscle mRNA indicates the mechanism of tissue specific ECM-mediated tissue repair may be immune and metabolism pathway-driven. Taken together, this suggests there is benefit in using tissue specific ECM for regenerative medicine applications.

scholarly journals Loss of Parkin Results in Altered Muscle Stem Cell Differentiation during Regeneration

2020 ◽  
Vol 21 (21) ◽  
pp. 8007
Author(s):  
Marcos V. Esteca ◽  
Matheus B. Severino ◽  
João G. Silvestre ◽  
Gustavo Palmeira dos Santos ◽  
Letícia Tamborlin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
High Capacity ◽  
Stem Cell Differentiation ◽  
Skeletal Muscle Regeneration ◽  
Post Injury ◽  
Cross Sectional ◽  
Myoblast Cell Line ◽  
Myoblast Cell

The high capacity of the skeletal muscle to regenerate is due to the presence of muscle stem cells (MuSCs, or satellite cells). The E3 ubiquitin ligase Parkin is a key regulator of mitophagy and is recruited to mitochondria during differentiation of mouse myoblast cell line. However, the function of mitophagy during regeneration has not been investigated in vivo. Here, we have utilized Parkin deficient (Parkin–/–) mice to investigate the role of Parkin in skeletal muscle regeneration. We found a persistent deficiency in skeletal muscle regeneration in Parkin–/– mice after cardiotoxin (CTX) injury with increased area of fibrosis and decreased cross-sectional area (CSA) of myofibres post-injury. There was also a significant modulation of MuSCs differentiation and mitophagic markers, with altered mitochondrial proteins during skeletal muscle regeneration in Parkin–/– mice. Our data suggest that Parkin-mediated mitophagy plays a key role in skeletal muscle regeneration and is necessary for MuSCs differentiation.

scholarly journals BMSC Transplantation Aggravates Inflammation, Oxidative Stress, and Fibrosis and Impairs Skeletal Muscle Regeneration

2019 ◽  
Vol 10 ◽  
Author(s):  
Xiaoguang Liu ◽  
Lifang Zheng ◽  
Yongzhan Zhou ◽  
Yingjie Chen ◽  
Peijie Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Skeletal Muscle Regeneration

Inactivation of PPARβ/δ adversely affects satellite cells and reduces postnatal myogenesis

2015 ◽  
Vol 309 (2) ◽  
pp. E122-E131 ◽  
Author(s):  
Preeti Chandrashekar ◽  
Ravikumar Manickam ◽  
Xiaojia Ge ◽  
Sabeera Bonala ◽  
Craig McFarlane ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Tibialis Anterior ◽  
Tibialis Anterior Muscle ◽  
Skeletal Muscle Regeneration ◽  
Muscle Weight ◽  
Cross Sectional ◽  
Postnatal Myogenesis

Peroxisome proliferator-activated receptor β/δ ( PPARβ/δ) is a ubiquitously expressed gene with higher levels observed in skeletal muscle. Recently, our laboratory showed (Bonala S, Lokireddy S, Arigela H, Teng S, Wahli W, Sharma M, McFarlane C, Kambadur R. J Biol Chem 287: 12935–12951, 2012) that PPARβ/δ modulates myostatin activity to induce myogenesis in skeletal muscle. In the present study, we show that PPARβ/δ-null mice display reduced body weight, skeletal muscle weight, and myofiber atrophy during postnatal development. In addition, a significant reduction in satellite cell number was observed in PPARβ/δ-null mice, suggesting a role for PPARβ/δ in muscle regeneration. To investigate this, tibialis anterior muscles were injured with notexin, and muscle regeneration was monitored on days 3, 5, 7, and 28 postinjury. Immunohistochemical analysis revealed an increased inflammatory response and reduced myoblast proliferation in regenerating muscle from PPARβ/δ-null mice. Histological analysis confirmed that the regenerated muscle fibers of PPARβ/δ-null mice maintained an atrophy phenotype with reduced numbers of centrally placed nuclei. Even though satellite cell numbers were reduced before injury, satellite cell self-renewal was found to be unaffected in PPARβ/δ-null mice after regeneration. Previously, our laboratory had showed (Bonala S, Lokireddy S, Arigela H, Teng S, Wahli W, Sharma M, McFarlane C, Kambadur R. J Biol Chem 287: 12935–12951, 2012) that inactivation of PPARβ/δ increases myostatin signaling and inhibits myogenesis. Our results here indeed confirm that inactivation of myostatin signaling rescues the atrophy phenotype and improves muscle fiber cross-sectional area in both uninjured and regenerated tibialis anterior muscle from PPARβ/δ-null mice. Taken together, these data suggest that absence of PPARβ/δ leads to loss of satellite cells, impaired skeletal muscle regeneration, and postnatal myogenesis. Furthermore, our results also demonstrate that functional antagonism of myostatin has utility in rescuing these effects.

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