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Platelet releasate promotes skeletal myogenesis by increasing muscle stem cell commitment to differentiation and accelerates muscle regeneration following acute injury
Aim: The use of platelets as biomaterials has gained intense research interest. However,
the mechanisms regarding platelet-mediated skeletal myogenesis remain to be established.
The aim of this study was to determine the role of platelet releasate in skeletal myogenesis
and muscle stem cell fate in vitro and ex vivo respectively.
Methods: We analysed the effect of platelet releasate on proliferation and differentiation of
C2C12 myoblasts by means of cell proliferation assays, immunohistochemistry, gene
expression and cell bioenergetics. We expanded in vitro findings on single muscle fibres by
determining the effect of platelet releasate on murine skeletal muscle stem cells using
protein expression profiles for key myogenic regulatory factors.
Results: TRAP6 and collagen used for releasate preparation had a more pronounced effect
on myoblast proliferation versus thrombin and sonicated platelets (P<0.05). In addition,
platelet concentration positively correlated with myoblast proliferation. Platelet releasate
increased myoblast and muscle stem cell proliferation in a dose-dependent manner, which
was mitigated by VEGFR and PDGFR inhibition. Inhibition of VEGFR and PDGFR ablated
MyoD expression on proliferating muscle stem cells, compromising their commitment to
differentiation in muscle fibres (P<0.001). Platelet releasate was detrimental for myoblast
fusion and affected differentiation of myoblasts in a temporal manner. Most importantly we
show that platelet releasate promotes skeletal myogenesis through the PDGF/VEGF-Cyclin
D1-MyoD-Scrib-Myogenin axis and accelerates skeletal muscle regeneration after acute
injury.
Conclusion: This study provides novel mechanistic insights on the role of platelet releasate
in skeletal myogenesis and set the physiological basis for exploiting platelets as biomaterials
in regenerative medicine
Functional analysis of an HSV-1 virulence factor.
Functional analysis of an HSV-1 virulence factor
Pharmacokinetics and use of desferrioxamine in the diagnosis and therapy of aluminium -overload
PGS7 COST ANALYSIS OF A NEW PROPOSAL FOR REIMBURSEMENT OF PROTON PUMP INHIBITOR TREATMENT OF GASTROESOPHAGEAL REFLUX DISEASE (GERD) IN BELGIUM
Inhibition of the matrix metalloproteinase system in a rat model of chronic cyclosporine nephropathy
Inhibition of the matrix metalloproteinase system in a rat model of chronic cyclosporine nephropathy.BackgroundChronic cyclosporine A (CsA)-induced nephropathy is histologically characterized by tubular lesions, the interstitial recruitment of inflammatory cells, arteriolopathy and focal interstitial fibrosis. Recent studies show that the intrarenal inhibition of matrix degradation and recruitment of monocytes/macrophages into the kidney plays a critical role in the development of renal interstitial fibrosis.MethodsWe examined the expression of components of the matrix metalloproteinase (MMP) system and plasminogen activator inhibitor type-1 (PAI-1) in kidneys from rats injected daily s.c. during three weeks with CsA (10, 15 or 20mg CsA/kg body wt) or vehicle solution.ResultsIn all CsA-treated rats, serum creatinine levels were significantly elevated compared to control levels. The extent of CsA-induced atrophy was not influenced by the dosage during a three-week CsA treatment. The administration of CsA did not significantly increase total cortical interstitial collagen deposition, whereas α-smooth muscle actin expression was significantly increased in all CsA-treated rats. Analysis of the different subpopulations of inflammatory cells recruited into the chronically injured kidney revealed a marked influx of macrophages into fibrotic cortical foci of CsA-treated rats. The number of cortical macrophages was highest in the group receiving the highest CsA dose. PAI-1 antigen, present in proximal tubular lysosomes in kidneys from all experimental groups, stained very intensely in atrophic tubules in CsA-treated rats. Both stromelysin and interstitial collagenase mRNA were expressed in the kidneys of control rats, but their message transcription remained unaltered after CsA treatment. In contrast, the expression of tissue inhibitor of matrix metalloproteinase type 1 (TIMP-1) was significantly increased after CsA treatment. TIMP-1 mRNA was undetectable in renal sections from sodium-depleted vehicle-treated animals using the in situ hybridization (ISH) technique. ISH of selected renal sections of CsA-treated rats identified the cells responsible for the increased TIMP-1 message transcription after CsA administration, mainly as interstitial cells and also as visceral and parietal epithelial cells.ConclusionsThese results suggest that the locally increased expression of TIMP-1 rather than a decrease of matrix metalloprotease expression, contributes to the development of CsA-induced focal interstitial fibrosis in the rat
Role of serotonin in the development of Chinese herbs nephropathy (CHN). Journal American Society of Nephrology, 9, 1998, 593 A.
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