Skeletal Muscle Injury Induces Hepatocyte Growth Factor Expression in Spleen

Suzuki, Shunichi; Yamanouchi, Keitaro; Soeta, Chie; Katakai, Yuko; Harada, Rie; Naito, Kunihiko; Tojo, Hideaki

doi:10.1006/bbrc.2002.6706

Cited by 40 publications

(30 citation statements)

References 35 publications

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“…23 In adult muscle as well as lung, liver, kidney, and spleen, HGF was found primarily in its inactive single-chain form, with the level of expression and activation increased after tissue injury. 22,45 In contrast, other studies have reported that HGF is found primarily in its active ␣-chain form in uninjured skeletal muscle. 46,47 The contrasting findings may be explained by differences in sample preparation.…”

Section: Org Frommentioning

confidence: 95%

“…21 HGF and c-met are also expressed in noninjured skeletal muscle of adult animals. 22,23 Although HGF expression is increased at both the mRNA and protein levels after muscle injury, 22,24 the precise role of this growth factor during muscle regeneration has not been established. Injection of exogenous HGF into noninjured muscle of rats activates quiescent satellite cells, 23 which are muscle precursor cells required for regeneration.…”

Section: Introductionmentioning

confidence: 99%

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Urokinase-type plasminogen activator increases hepatocyte growth factor activity required for skeletal muscle regeneration

Sisson

Nguyen

et al. 2009

Blood

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The plasminogen system plays a crucial role in the repair of a variety of tissues, including skeletal muscle. We hypothesized that urokinase-type plasminogen activator (uPA) promotes muscle regeneration by activating hepatocyte growth factor (HGF), which, in turn, stimulates proliferation of myoblasts required for regeneration. In our studies, levels of active HGF and phosphorylation of the HGF receptor c-met were increased after muscle injury in wild-type mice. Compared with wild-type animals, mice deficient in uPA (uPA ؊/؊ ) had markedly reduced HGF levels and c-met activation after muscle damage. This reduced HGF activity in uPA ؊/؊ animals was associated with decreased cell proliferation, myoblast accumulation, and new muscle fiber formation. On the other hand, HGF activity was enhanced at early time points in PAI-1 ؊/؊ mice compared with wild-type mice and the PAI-1 ؊/؊ animals exhibited accelerated muscle fiber regeneration. Furthermore, administration of exogenous uPA rescued HGF levels and muscle regeneration in uPA ؊/؊ mice, and an HGF-blocking antibody reduced HGF activity and muscle regeneration in wildtype mice. We also found that uPA promotes myoblast proliferation in vitro through its proteolytic activity, and this process was inhibited by an HGFblocking antibody. Together, our findings demonstrate that uPA promotes muscle regeneration through HGF activation and subsequent myoblast proliferation. IntroductionThe plasminogen system plays a crucial role in the repair of a variety of tissues. This extracellular serine protease cascade includes the urokinase-type plasminogen activator (uPA) and its primary inhibitor, plasminogen activator inhibitor-1 (PAI-1). The classic function of uPA is to cleave plasminogen to form active plasmin, a broad-spectrum protease with activity toward a variety of extracellular matrix molecules. 1,2 Genetic manipulations that inhibit plasminogen activation lead to impaired healing of lung, liver, kidney, and skin. [3][4][5][6] Similarly, mice deficient in uPA or plasminogen demonstrate markedly impaired muscle regeneration. [7][8][9] In contrast, mice lacking PAI-1 exhibit accelerated muscle regeneration. 7 Despite its robust effect on skeletal muscle regeneration, the molecular mechanisms by which the plasminogen system regulates this process remain largely undefined. Clearance of the provisional fibrin matrix that is deposited after muscle injury may be one mechanism by which uPA promotes regeneration. 8 However, uPA may also promote tissue repair through other pathways, such as the proteolytic activation of growth factors, including hepatocyte growth factor (HGF). HGF is synthesized and secreted as an inactive single-chain molecule, and proteolytic cleavage results in formation of the active 2-chain form, which has affinity for the c-met receptor. [10][11][12] uPA is one of a select group of proteases known to activate HGF, 11,12 the others being tissue-type plasminogen activator, factor XIa, factor XIIa, matriptase, and HGF activator. [13][14][15] In addition, uPA app...

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Section: Org Frommentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Urokinase-type plasminogen activator increases hepatocyte growth factor activity required for skeletal muscle regeneration

Sisson

Nguyen

et al. 2009

Blood

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“…In vitro and in vivo data have revealed that release of nitric oxide synthase (NOS) from the basal lamina after myofiber stretch or damage leads to the production of nitric oxide (NO), which in turn activates MMPs and release HGF from local HSPGs (522,523,576). Alternatively, the observed rapid upregulation of HGF following muscle injury is due to release of HGF from intact organs, such as the spleen (513).…”

Section: Ecm and Associated Factorsmentioning

confidence: 99%

Satellite Cells and the Muscle Stem Cell Niche

Yin

Price

Rudnicki

2013

Physiological Reviews

1,715

1,808

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LYin H, Price F, Rudnicki MA. Satellite Cells and the Muscle Stem Cell Niche. Physiol Rev 93: 23-67, 2013; doi:10.1152/physrev.00043.2011.-Adult skeletal muscle in mammals is a stable tissue under normal circumstances but has remarkable ability to repair after injury. Skeletal muscle regeneration is a highly orchestrated process involving the activation of various cellular and molecular responses. As skeletal muscle stem cells, satellite cells play an indispensible role in this process. The self-renewing proliferation of satellite cells not only maintains the stem cell population but also provides numerous myogenic cells, which proliferate, differentiate, fuse, and lead to new myofiber formation and reconstitution of a functional contractile apparatus. The complex behavior of satellite cells during skeletal muscle regeneration is tightly regulated through the dynamic interplay between intrinsic factors within satellite cells and extrinsic factors constituting the muscle stem cell niche/microenvironment. For the last half century, the advance of molecular biology, cell biology, and genetics has greatly improved our understanding of skeletal muscle biology. Here, we review some recent advances, with focuses on functions of satellite cells and their niche during the process of skeletal muscle regeneration.

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“…The effects of HGF in SCs quiescence appears to be the work of a concentration-dependent negativefeedback mechanism, promoting activation and proliferation at low concentrations, while rebooting SCs to quiescence and promoting muscle-specific proteins expression in increasing concentrations [117]. It is present in the undamaged muscle and is released upon injury [118], mainly of physical/mechanical nature [117], and it is also released from other organs, such as the liver and spleen, acting on skeletal muscle tissue in an endocrine way [119]. Its effects are observed in a restricted time window, peaking for the first days following injury and then decreasing.…”

Section: The Role Of Growth Factors and Cytokines In Skeletal Muscle mentioning

confidence: 99%

Trends in Mesenchymal Stem Cells' Applications for Skeletal Muscle Repair and Regeneration

Caseiro¹,

Pereira²,

Bártolo³

et al. 2015

Progress in Stem Cell Transplantation

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Skeletal muscle injuries are quite frequent in traumatic scenarios, such as war injuries or road-or work-related accidents. The skeletal muscle has good regenerative ability, but the extent or recurrence of muscle injury might impair complete structural and functional recovery. Severe tissue loss overwhelms skeletal muscle´s intrinsic regenerative capabilities and culminates in the development of noncontractile fibrous tissue scar. Conservative RICE -based and surgical treatments show limited efficacy in terms of improving these severe cases outcomes, pressing the need for new approaches on skeletal muscle's therapy. Since the first suggestions of the potential of mesenchymal stem cells for regenerative medicine and tissue engineering, many applications have been explored for a variety of tissues and diseases, including the skeletal muscle, which is the focus of this literature review.

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Skeletal Muscle Injury Induces Hepatocyte Growth Factor Expression in Spleen

Cited by 40 publications

References 35 publications

Urokinase-type plasminogen activator increases hepatocyte growth factor activity required for skeletal muscle regeneration

Urokinase-type plasminogen activator increases hepatocyte growth factor activity required for skeletal muscle regeneration

Satellite Cells and the Muscle Stem Cell Niche

Trends in Mesenchymal Stem Cells' Applications for Skeletal Muscle Repair and Regeneration

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