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Serpin A1 and the modulation of type I collagen turnover: Effect of the C-terminal peptide 409-418 (SA1-III) in human dermal fibroblasts.

Abstract：

:The pharmacological modulation of collagen turnover is a strategy potentially useful in different skin conditions. The serine protease inhibitor Serpin A1 and portions of its C-terminal region have been investigated as collagen modulators. To clarify the mechanisms by which the C-terminal 409-418 peptide SA1-III increases extracellular type I collagen levels, to compare its activities range with that of the originator molecule Serpin A1, and to evaluate its efficacy in primary cultures from adult and aged human subjects. The different forms of type I collagen were analyzed by means of western blot in cell lysates and cell-conditioned media of primary human dermal fibroblasts obtained from subjects of different ages. Gelatin zymography was used to investigate the degrading enzymes. Cell viability and in vitro wound healing tests were used to evaluate cell proliferation. The SA1-III peptide increased extracellular collagen levels by reducing degradation, with no effect on cellular biosynthesis or cell proliferation mechanisms. A reduced level of MMP-2 and MMP-9 was also found in cell media upon peptide treatment. No peptide effect was detected on inflammatory mediators gene expression in resting and LPS-stimulated fibroblasts, or in the wound healing test. The SA1-III peptide is a good collagen modulator candidate, protecting collagen against degradation without detectable actions on biosynthesis, acting at reasonably low concentrations, and non-interfering with cell proliferation. It is effective in primary fibroblasts from young and aged subjects. These effects can prove useful in pathological and physiological skin conditions in which collagen degradation is excessive compared to the synthetic capacity.

journal_name

Cell Biol Int

journal_title

Cell biology international

authors

Cipriani C,Pascarella S,Errante F,Menicacci B,Magnelli L,Mocali A,Rovero P,Giovannelli L

doi

10.1002/cbin.11018

subject

Has Abstract

pub_date

2018-09-01 00:00:00

pages

1340-1348

issue

eissn

1065-6995

issn

1095-8355

journal_volume

pub_type

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Serpin A1 and the modulation of type I collagen turnover: Effect of the C-terminal peptide 409-418 (SA1-III) in human dermal fibroblasts.