SPARC Interacts with Actin in Skeletal Muscle in Vitro and in Vivo

Jørgensen, Louise Helskov; Jepsen, Pia Lørup; Boysen, Anders; Dalgaard, Line Barner; Hvid, Lars G.; Ørtenblad, Niels; Ravn, Dea; Sellathurai, Jeeva; Møller‐Jensen, Jakob; Lochmüller, Hanns; Schrøder, Henrik Daa

doi:10.1016/j.ajpath.2016.10.013

Cited by 35 publications

(26 citation statements)

References 47 publications

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“…In aggressive tumor phenotypes, SPARC may act as a positive regulator of metastatic potential by augmenting vascular permeability [84]. Persistent induction of SPARC promotes tissue fibrosis, nephropathy, retinopathy, and non-alcoholic fatty liver disease, while its deletion/inhibition protects against the same [85–87]. Considering that circulating SPARC is up-regulated in metabolic disease, accelerated aging conditions (Werner Syndrome etc.…”

Section: Resultsmentioning

confidence: 99%

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Lifelong aerobic exercise protects against inflammaging and cancer

et al. 2019

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Biological aging is associated with progressive damage accumulation, loss of organ reserves, and systemic inflammation ('inflammaging'), which predispose for a wide spectrum of chronic diseases, including several types of cancer. In contrast, aerobic exercise training (AET) reduces inflammation, lowers all-cause mortality, and enhances both health and lifespan. In this study, we examined the benefits of early-onset, lifelong AET on predictors of health, inflammation, and cancer incidence in a naturally aging mouse model (C57BL/J6). Lifelong, voluntary wheel-running (O-AET; 26-month-old) prevented age-related declines in aerobic fitness and motor coordination vs. age-matched, sedentary controls (O-SED). AET also provided partial protection against sarcopenia, dynapenia, testicular atrophy, and overall organ pathology, hence augmenting the ‘physiologic reserve’ of lifelong runners. Systemic inflammation, as evidenced by a chronic elevation in 17 of 18 pro- and anti-inflammatory cytokines and chemokines (P < 0.05 O-SED vs. 2-month-old Y-CON), was potently mitigated by lifelong AET (P < 0.05 O-AET vs. O-SED), including master regulators of the cytokine cascade and cancer progression (IL-1β, TNF-α, and IL-6). In addition, circulating SPARC, previously known to be upregulated in metabolic disease, was elevated in old, sedentary mice, but was normalized to young control levels in lifelong runners. Remarkably, malignant tumours were also completely absent in the O-AET group, whereas they were present in the brain (pituitary), liver, spleen, and intestines of sedentary mice. Collectively, our results indicate that early-onset, lifelong running dampens inflammaging, protects against multiple cancer types, and extends healthspan of naturally-aged mice.

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Section: Resultsmentioning

confidence: 99%

“…Considering that circulating SPARC is up-regulated in metabolic disease, accelerated aging conditions (Werner Syndrome etc. ), and in sarcopenia [85, 88–93], it is conceivable that it may be used as a general biomarker of advancing age and/or pathological aging processes.…”

Section: Resultsmentioning

confidence: 99%

Lifelong aerobic exercise protects against inflammaging and cancer

et al. 2019

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“…8 ) myoblasts in mice. Recent studies showed that SPARC affects the differentiation of human muscle cells by regulating cytoskeletal remodeling 9,10 .…”

Section: Introductionmentioning

confidence: 99%

SPARCL1 promotes C2C12 cell differentiation via BMP7-mediated BMP/TGF-β cell signaling pathway

et al. 2019

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The extracellular matrix (ECM) is known to regulate tissue development and cell morphology, movement, and differentiation. SPARCL1 is an ECM protein, but its role in mouse cell differentiation has not been widely investigated. The results of western blotting and immunofluorescence showed that SPARCL1 is associated with the repair of muscle damage in mice and that SPARCL1 binds to bone morphogenetic protein 7 (BMP7) by regulating BMP/transforming growth factor (TGF)-β cell signaling. This pathway promotes the differentiation of C2C12 cells. Using CRISPR/Cas9 technology, we also showed that SPARCL1 activates BMP/TGF-β to promote the differentiation of C2C12 cells. BMP7 molecules were found to interact with SPARCL1 by immunoprecipitation analysis. Western blotting and immunofluorescence were performed to verify the effect of BMP7 on C2C12 cell differentiation. Furthermore, SPARCL1 was shown to influence the expression of BMP7 and activity of the BMP/TGF-β signaling pathway. Finally, SPARCL1 activation was accompanied by BMP7 inhibition in C2C12 cells, which confirmed that SPARCL1 affects BMP7 expression and can promote C2C12 cell differentiation through the BMP/TGF-β pathway. The ECM is essential for muscle regeneration and damage repair. This study intends to improve the understanding of the molecular mechanisms of muscle development and provide new treatment ideas for muscle injury diseases.

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“…Car3 is a muscle-specific carbonic anhydrase 33 . Sparc is a secreted muscle protein 34,35 . Pfkfb3 is transcriptionally regulated via p38 pathway following stress and functions in glycolysis 36,37 .…”

Section: Discussionmentioning

confidence: 99%

Deletion of metal transporter Zip14 (Slc39a14) produces skeletal muscle wasting, endotoxemia, Mef2c activation and induction of miR-675 and Hspb7

Kim

Aydemir

Jimenez

et al. 2020

Sci Rep

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Skeletal muscle represents the largest pool of body zinc, however, little is known about muscle zinc homeostasis or muscle-specific zinc functions. Zip14 (Slc39a14) was the most highly expressed zinc transporter in skeletal muscle of mice in response to LPS-induced inflammation. We compared metabolic parameters of skeletal muscle from global Zip14 knockout (KO) and wild-type mice (WT). At basal steady state Zip14 Ko mice exhibited a phenotype that included muscle wasting and metabolic endotoxemia. Microarray and qpcR analysis of gastrocnemius muscle RnA revealed that ablation of Zip14 produced increased muscle p-Mef2c, Hspb7 and miR-675-5p expression and increased p38 activation. chip assays showed enhanced binding of nf-κβ to the Mef2c promoter. in contrast, LpSinduced systemic inflammation enhanced Zip14-dependent zinc uptake by muscle, increased expression of Atrogin1 and MuRF1 and markedly reduced MyoD. these signatures of muscle atrophy and cachexia were not influenced by Zip14 ablation, however. LpS-induced miR-675-3p and-5p expression was Zip14-dependent. Collectively, these results with an integrative model are consistent with a Zip14 function in skeletal muscle at steady state that supports myogenesis through suppression of metabolic endotoxemia and that Zip14 ablation coincides with sustained activity of phosphorylated components of signaling pathways including p-Mef2c, which causes Hspb7-dependent muscle wasting.

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SPARC Interacts with Actin in Skeletal Muscle in Vitro and in Vivo

Cited by 35 publications

References 47 publications

Lifelong aerobic exercise protects against inflammaging and cancer

Lifelong aerobic exercise protects against inflammaging and cancer

SPARCL1 promotes C2C12 cell differentiation via BMP7-mediated BMP/TGF-β cell signaling pathway

Deletion of metal transporter Zip14 (Slc39a14) produces skeletal muscle wasting, endotoxemia, Mef2c activation and induction of miR-675 and Hspb7

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