N-acetyl-seryl-aspartyl-lysyl-proline attenuates renal inflammation and tubulointerstitial fibrosis in rats

Wang, Mingao; Liu, Ruichan; Jia, Xibei; Mu, Suhong; Xie, Ruiqin

doi:10.3892/ijmm_00000527

Cited by 13 publications

(2 citation statements)

References 30 publications

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“…Kanasaki et al showed that in human mesangial cells, Ac-SDKP inhibited the TGF-β-induced expression of PAI-1, Smad2 phosphorylation, and promoted the translocation of Smad7 from the cytoplasm to nucleus, which inhibited R-Smad proteins [ 61 ]. Wang et al reported that in UUO rats, Ac-SDKP treatment relieved interstitial fibrosis through the downregulation of TGF-β and α-SMA [ 62 ]. Chan et al reported that in UUO BALB/c mice, the level of AC-SDKP in urine was elevated by captopril treatment and reduced with co-treatment of captopril and S17092.…”

Section: Kidneymentioning

confidence: 99%

The Role of Tβ4-POP-Ac-SDKP Axis in Organ Fibrosis

Wang

Jia

Zhang

2022

IJMS

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Fibrosis is a pathological process in which parenchymal cells are necrotic and excess extracellular matrix (ECM) is accumulated due to dysregulation of tissue injury repair. Thymosin β4 (Tβ4) is a 43 amino acid multifunctional polypeptide that is involved in wound healing. Prolyl oligopeptidase (POP) is the main enzyme that hydrolyzes Tβ4 to produce its derivative N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) which is found to play a role in the regulation of fibrosis. Accumulating evidence suggests that the Tβ4-POP-Ac-SDKP axis widely exists in various tissues and organs including the liver, kidney, heart, and lung, and participates in the process of fibrogenesis. Herein, we aim to elucidate the role of Tβ4-POP-Ac-SDKP axis in hepatic fibrosis, renal fibrosis, cardiac fibrosis, and pulmonary fibrosis, as well as the underlying mechanisms. Based on this, we attempted to provide novel therapeutic strategies for the regulation of tissue damage repair and anti-fibrosis therapy. The Tβ4-POP-Ac-SDKP axis exerts protective effects against organ fibrosis. It is promising that appropriate dosing regimens that rely on this axis could serve as a new therapeutic strategy for alleviating organ fibrosis in the early and late stages.

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Section: Kidneymentioning

confidence: 99%

The Role of Tβ4-POP-Ac-SDKP Axis in Organ Fibrosis

Wang

Jia

Zhang

2022

IJMS

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“…In particular, ( N ‐acetyl‐SDKP) reduces the expression of inflammatory molecules monocyte chemoattractant protein‐1 (MCP‐1), which is one of the most important indicators of the inflammatory process within the renal tubular tissue. This reducing action is correlated with the activation of nuclear factor‐kappa‐B (NF‐κB) (Nussberger et al, 1998b; Wang et al, 2010; Yacoub & Campbell, 2015). Consequently, the antihypertensive behavior of ACE‐1 inhibitors is controlled by selective C ‐ACE domain inhibition; in expense of reduction in antifibrotic activity due to clearance of the active antifibrotic agent ( N ‐acetyl‐SDKP) through unblocked ACE N ‐domain (Cotton et al, 2002; Fuchs et al, 2008; Sharma et al, 2008; Zuo et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Vicinal diaryl pyrazole with tetrazole/urea scaffolds as selective angiotensin converting enzyme‐1/cyclooxygenase‐2 inhibitors: Design, synthesis, anti‐hypertensive, anti‐fibrotic, and anti‐inflammatory

Fadaly,

Elshaier,

Ali

et al. 2024

Drug Development Research

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As a hybrid weapon, two novel series of pyrazoles, 16a‐f and 17a‐f, targeting both COX‐2 and ACE‐1‐N‐domain, were created and their anti‐inflammatory, anti‐hypertensive, and anti‐fibrotic properties were evaluated. In vitro, 17b and 17f showed COX‐2 selectivity (SI = 534.22 and 491.90, respectively) compared to celecoxib (SI = 326.66) and NF‐κB (IC50 1.87 and 2.03 μM, respectively). 17b (IC50 0.078 μM) and 17 f (IC50 0.094 μM) inhibited ACE‐1 comparable to perindopril (PER) (IC50 0.048 μM). In vivo, 17b decreased systolic blood pressure by 18.6%, 17b and 17f increased serum NO levels by 345.8%, and 183.2%, respectively, increased eNOS expression by 0.97 and 0.52 folds, respectively and reduced NF‐κB‐p65 and P38‐MAPK expression by −0.62, −0.22, −0.53, and −0.24 folds, respectively compared to l‐NAME (−0.34, −0.45 folds decline in NF‐κB‐p65 and P38‐MAPK, respectively). 17b reduced ANG‐II expression which significantly reversed the cardiac histological changes induced by L‐NAME.

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Engineered M13 Nanofiber Accelerates Ischemic Neovascularization by Enhancing Endothelial Progenitor Cells

Lee

Kim

et al. 2017

Tissue Eng Regen Med

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Dysfunction or loss of blood vessel causes several ischemic diseases. Although endothelial progenitor cells (EPCs) are a promising source for cell-based therapy, ischemia-induced pathophysiological condition limits the recovery rate by causing drastic cell death. To overcome this issue, we attempted to develop a cell-targeted peptide delivery and priming system to enhance EPCbased neovascularization using an engineered M13 bacteriophage harboring nanofibrous tubes displaying *2700 multiple functional motifs. The M13 nanofiber was modified by displaying RGD, which is an integrin-docking peptide, on the minor coat protein, and by mutilayering SDKP motifs, which are the key active sites for thymosin b4, on the major coat protein. The engineered M13 nanofiber dramatically enhanced ischemic neovascularization by activating intracellular and extracellular processes such as proliferation, migration, and tube formation in the EPCs. Furthermore, transplantation of the primed EPCs with the M13 nanofiber harboring RGD and SDKP facilitated functional recovery and neovascularization in a murine hindlimb ischemia model. Overall, this study demonstrates the effectiveness of the M13 nanofiber-based novel peptide delivery and priming strategy in promoting EPC bioactivity and neovessel regeneration. To our knowledge, this is first report on M13 nanofibers harboring dual functional motifs, the use of which might be a novel strategy for stem and progenitor cell therapy against cardiovascular ischemic diseases. Keywords M13 bacteriophage Á Endothelial progenitor cell Á RGD Á SDKP Á Neovascularization Electronic supplementary material The online version of this article (

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N-acetyl-seryl-aspartyl-lysyl-proline attenuates renal inflammation and tubulointerstitial fibrosis in rats

Cited by 13 publications

References 30 publications

The Role of Tβ4-POP-Ac-SDKP Axis in Organ Fibrosis

The Role of Tβ4-POP-Ac-SDKP Axis in Organ Fibrosis

Vicinal diaryl pyrazole with tetrazole/urea scaffolds as selective angiotensin converting enzyme‐1/cyclooxygenase‐2 inhibitors: Design, synthesis, anti‐hypertensive, anti‐fibrotic, and anti‐inflammatory

Engineered M13 Nanofiber Accelerates Ischemic Neovascularization by Enhancing Endothelial Progenitor Cells

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