The tetrapeptide AcSDKP, an inhibitor of primitive hematopoietic cell proliferation, induces angiogenesis in vitro and in vivo

Liu, Jian‐Miao; Lawrence, Françoise; Kovacevic, M.; Bignon, Jérôme; Papadimitriou, Evangelia; Lallemand, Jean‐Yves; Katsoris, Panagiotis; Potìer, Pierre; Fromes, Yves; Wdzieczak‐Bakala, Joanna

doi:10.1182/blood-2002-07-2315

Cited by 73 publications

(75 citation statements)

References 57 publications

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“…Ac-SDKP, likely by blocking inflammatory effects of Gal-3, prevents the lectin's detrimental effects on both cardiac remodeling and dysfunction. Ac-SDKP also promotes angiogenesis (16). Our laboratory previously found that Ac-SDKP stimulated endothelial cell proliferation, migration, and tube formation in vitro and increased myocardial capillary density in vivo (41).…”

Section: Discussionmentioning

confidence: 96%

N-acetyl-seryl-aspartyl-lysyl-proline prevents cardiac remodeling and dysfunction induced by galectin-3, a mammalian adhesion/growth-regulatory lectin

Liu¹,

D’Ambrosio²,

Liao³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

250

184

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Section: Discussionmentioning

confidence: 96%

N-acetyl-seryl-aspartyl-lysyl-proline prevents cardiac remodeling and dysfunction induced by galectin-3, a mammalian adhesion/growth-regulatory lectin

Liu¹,

D’Ambrosio²,

Liao³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

250

184

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“…Ac-SDKP, the product of T␤4 hydrolysis by meprin-␣ and POP, shares very similar properties with meprin-␣. It has been reported that Ac-SDKP promotes angiogenesis in cornea (43) and abdominal wall of the rat (26). The anti-inflammatory properties of Ac-SDKP have been shown in pathologies such as renal diseases, hypertension, and cardiovascular diseases (31,45).…”

Section: Discussionmentioning

confidence: 99%

“…The antifibrotic, anti-inflammatory, and angiogenic properties of Ac-SDKP have been demonstrated in the pathology of hypertension, heart, renal, diabetes, lung, and liver and in autoimmune diseases (7,12,14,26,33,44,45). However, the mechanism of Ac-SDKP release is not completely understood.…”

Section: Discussionmentioning

confidence: 99%

The anti-inflammatory peptide Ac-SDKP is released from thymosin-β4 by renal meprin-α and prolyl oligopeptidase

Kumar

Nakagawa

Janic

et al. 2016

American Journal of Physiology-Renal Physiology

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The anti-inflammatory peptide Ac-SDKP is released from thymosin-␤4 by renal meprin-␣ and prolyl oligopeptidase. Am J Physiol Renal Physiol 310: F1026 -F1034, 2016. First published March 9, 2016 doi:10.1152/ajprenal.00562.2015.-N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a natural tetrapeptide with antiinflammatory and antifibrotic properties. Previously, we have shown that prolyl oligopeptidase (POP) is involved in the Ac-SDKP release from thymosin-␤4 (T␤4). However, POP can only hydrolyze peptides shorter than 30 amino acids, and T␤4 is 43 amino acids long. This indicates that before POP hydrolysis takes place, T␤4 is hydrolyzed by another peptidase that releases NH2-terminal intermediate peptide(s) with fewer than 30 amino acids. Our peptidase database search pointed out meprin-␣ metalloprotease as a potential candidate. Therefore, we hypothesized that, prior to POP hydrolysis, T␤4 is hydrolyzed by meprin-␣. In vitro, we found that the incubation of T␤4 with both meprin-␣ and POP released Ac-SDKP, whereas no Ac-SDKP was released when T␤4 was incubated with either meprin-␣ or POP alone. Incubation of T␤4 with rat kidney homogenates significantly released Ac-SDKP, which was blocked by the meprin-␣ inhibitor actinonin. In addition, kidneys from meprin-␣ knockout (KO) mice showed significantly lower basal Ac-SDKP amount, compared with wild-type mice. Kidney homogenates from meprin-␣ KO mice failed to release Ac-SDKP from T␤4. In vivo, we observed that rats treated with the ACE inhibitor captopril increased plasma concentrations of Ac-SDKP, which was inhibited by the coadministration of actinonin (vehicle, 3.1 Ϯ 0.2 nmol/l; captopril, 15.1 Ϯ 0.7 nmol/l; captopril ϩ actinonin, 6.1 Ϯ 0.3 nmol/l; P Ͻ 0.005). Similar results were obtained with urinary Ac-SDKP after actinonin treatment. We conclude that release of Ac-SDKP from T␤4 is mediated by successive hydrolysis involving meprin-␣ and POP.N-acetyl-seryl-aspartyl-lysyl-proline; thymosin-␤4; meprin-␣; prolyl oligopeptidase; angiotensin-converting enzyme THE ANTI-INFLAMMATORY PEPTIDE N-acetyl-seryl-aspartyl-lysylproline (Ac-SDKP) was identified originally in the bone marrow (24). It has also been widely distributed in mammalian organs, plasma, urine, and circulating mononuclear cells (23,39,46). In animal diseases with hypertension, as well as cardiovascular and kidney disease, Ac-SDKP reduces inflammatory cell infiltration and collagen deposition in the heart, kidney, lung, and liver (14,15,33,34,37,44). Ac-SDKP is hydrolyzed by angiotensin-converting enzyme (ACE) and has a short half-life of 4.5 min in the circulation (16). Treatment with ACE inhibitors significantly increased plasma concentration of Ac-SDKP (2), and some of the ACE inhibitors protective effects were reported to be mediated by the increases in Ac-SDKP concentrations (34, 35).Thymosin-␤4 (T␤4) is a major G-actin-sequestering peptide that consists of 43 amino acids. Since it contains the Ac-SDKP sequence in its NH 2 -terminal, T␤4 is considered to be the precursor of 39). Our group has shown p...

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“…Intracellular AcSDKP was measured using the AcSDKP enzyme immunoassay kit (Bertin Pharma, Montigny-le-Bretonneux, France) modified for the cells (29,39). In brief, cells were lysed with RIPA buffer containing 10 µmol/l captopril and 1 mmol/l PMSF.…”

Section: Reverse-transcription Quantitative Polymerase Chain Reactionmentioning

confidence: 99%

Prolyl oligopeptidase attenuates hepatic stellate cell activation through induction of Smad7 and PPAR-γ

Zhou

Wang

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Prolyl oligopeptidase (POP) is a serine endopeptidase widely distributed in vivo with high activity in the liver. However, its biological functions in the liver have remained largely elusive. A previous study by our group has shown that POP produced N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) and thereby exerted an anti-fibrogenic effect on hepatic stellate cells (HSCs) in vitro. It was therefore hypothesized that POP may affect the activation state of HSCs and has an important role in liver fibrosis. The HSC-T6 immortalized rat liver stellate cell line was treated with the POP inhibitor S17092 or transfected with recombinant lentivirus to overexpress POP. Cell proliferation and apoptosis were determined using a Cell Counting Kit-8 and flow cytometry, respectively. The activation status of HSCs was determined by examination of the expression of α-smooth muscle actin (α-SMA), collagen I, monocyte chemoattractant protein-1 (MCP-1), transforming growth factor (TGF)-β-Smad signaling and peroxisome proliferator activated receptor-γ (PPAR-γ). Inhibition by S17092 decreased, whereas lentiviral expression increased the activity of POP and cell proliferation, while neither of the treatments affected cell apoptosis. Of note, S17092 significantly increased, whereas POP overexpression decreased the expression of α-SMA and MCP-1 without affecting the expression of collagen I and TGF-β1. Furthermore, S17092 caused a reduction, whereas POP overexpression caused an upregulation of Smad7 protein and PPAR-γ, but not phosphorylated-Smad2/3 expression. In conclusion, POP attenuated the activation of HSCs through inhibition of TGF-β signaling and induction of PPAR-γ, which may have therapeutic potential in liver fibrosis.

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The tetrapeptide AcSDKP, an inhibitor of primitive hematopoietic cell proliferation, induces angiogenesis in vitro and in vivo

Cited by 73 publications

References 57 publications

N-acetyl-seryl-aspartyl-lysyl-proline prevents cardiac remodeling and dysfunction induced by galectin-3, a mammalian adhesion/growth-regulatory lectin

N-acetyl-seryl-aspartyl-lysyl-proline prevents cardiac remodeling and dysfunction induced by galectin-3, a mammalian adhesion/growth-regulatory lectin

The anti-inflammatory peptide Ac-SDKP is released from thymosin-β4 by renal meprin-α and prolyl oligopeptidase

Prolyl oligopeptidase attenuates hepatic stellate cell activation through induction of Smad7 and PPAR-γ

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