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A lipocalin-derived Peptide modulating fibroblasts and extracellular matrix proteins.

Carrijo-Carvalho LC, Maria DA, Ventura JS, Morais KL, Melo RL, Rodrigues CJ, Chudzinski-Tavassi AM - J Toxicol (2012)

Bottom Line: Interestingly, these proteins are found abundant in the venom of the Lonomia obliqua caterpillar.Results indicate that modulation effects displayed by lipocalins through this sequence motif involve cell survival, extracellular matrix remodeling, and cytokine signaling.Such effects can be related to the lipocalin roles in disease, development, and tissue repair.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Biochemistry and Biophysics, Butantan Institute, Avenida Vital Brasil 1500, 05503-900 São Paulo, SP, Brazil.

ABSTRACT
Lipocalin family members have been implicated in development, regeneration, and pathological processes, but their roles are unclear. Interestingly, these proteins are found abundant in the venom of the Lonomia obliqua caterpillar. Lipocalins are β-barrel proteins, which have three conserved motifs in their amino acid sequence. One of these motifs was shown to be a sequence signature involved in cell modulation. The aim of this study is to investigate the effects of a synthetic peptide comprising the lipocalin sequence motif in fibroblasts. This peptide suppressed caspase 3 activity and upregulated Bcl-2 and Ki-67, but did not interfere with GPCR calcium mobilization. Fibroblast responses also involved increased expression of proinflammatory mediators. Increase of extracellular matrix proteins, such as collagen, fibronectin, and tenascin, was observed. Increase in collagen content was also observed in vivo. Results indicate that modulation effects displayed by lipocalins through this sequence motif involve cell survival, extracellular matrix remodeling, and cytokine signaling. Such effects can be related to the lipocalin roles in disease, development, and tissue repair.

No MeSH data available.


Related in: MedlinePlus

Peptide treatment increases collagen in the mice dermis. (a) Mean values of groups treated with a single dose (0.2 mL, 1.15 μM pm2b, i.d.) or repeated doses compared with controls (n = 4–6). (b) Matched observations of pm2b-treated and saline-treated sites (1 × 1 cm) in the same animals in successive intervals after treatment. (c) Picrosirius-red-stained sections (originally 340x). Data are representative images and expressed as mean ± SEM. **P < 0.01, *P < 0.05 versus control.
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fig3: Peptide treatment increases collagen in the mice dermis. (a) Mean values of groups treated with a single dose (0.2 mL, 1.15 μM pm2b, i.d.) or repeated doses compared with controls (n = 4–6). (b) Matched observations of pm2b-treated and saline-treated sites (1 × 1 cm) in the same animals in successive intervals after treatment. (c) Picrosirius-red-stained sections (originally 340x). Data are representative images and expressed as mean ± SEM. **P < 0.01, *P < 0.05 versus control.

Mentions: Since the peptide treatment induced a change in the content of ECM proteins in vitro, we assessed whether if pm2b was also able to increase the amount of collagen in vivo in the mice dermis (Figure 3). Interaction of pm2b treatment and the collagen content was statistically significant (two-way ANOVA, P < 0.05), either if it was lower than that observed in vitro. Treatment with a single dose induced a mean increase of local collagen fibrils in about 10%, while with two repeated doses the mean increase was 15% (Figure 3(a)). With a single dose, the higher difference to controls was observed 7 days after treatment. The ratio between treated area and control dropped along the time. Interestingly, in the group treated with 2 doses of pm2b, the collagen increase lasted for 3 months (Figure 3(b)).


A lipocalin-derived Peptide modulating fibroblasts and extracellular matrix proteins.

Carrijo-Carvalho LC, Maria DA, Ventura JS, Morais KL, Melo RL, Rodrigues CJ, Chudzinski-Tavassi AM - J Toxicol (2012)

Peptide treatment increases collagen in the mice dermis. (a) Mean values of groups treated with a single dose (0.2 mL, 1.15 μM pm2b, i.d.) or repeated doses compared with controls (n = 4–6). (b) Matched observations of pm2b-treated and saline-treated sites (1 × 1 cm) in the same animals in successive intervals after treatment. (c) Picrosirius-red-stained sections (originally 340x). Data are representative images and expressed as mean ± SEM. **P < 0.01, *P < 0.05 versus control.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3379166&req=5

fig3: Peptide treatment increases collagen in the mice dermis. (a) Mean values of groups treated with a single dose (0.2 mL, 1.15 μM pm2b, i.d.) or repeated doses compared with controls (n = 4–6). (b) Matched observations of pm2b-treated and saline-treated sites (1 × 1 cm) in the same animals in successive intervals after treatment. (c) Picrosirius-red-stained sections (originally 340x). Data are representative images and expressed as mean ± SEM. **P < 0.01, *P < 0.05 versus control.
Mentions: Since the peptide treatment induced a change in the content of ECM proteins in vitro, we assessed whether if pm2b was also able to increase the amount of collagen in vivo in the mice dermis (Figure 3). Interaction of pm2b treatment and the collagen content was statistically significant (two-way ANOVA, P < 0.05), either if it was lower than that observed in vitro. Treatment with a single dose induced a mean increase of local collagen fibrils in about 10%, while with two repeated doses the mean increase was 15% (Figure 3(a)). With a single dose, the higher difference to controls was observed 7 days after treatment. The ratio between treated area and control dropped along the time. Interestingly, in the group treated with 2 doses of pm2b, the collagen increase lasted for 3 months (Figure 3(b)).

Bottom Line: Interestingly, these proteins are found abundant in the venom of the Lonomia obliqua caterpillar.Results indicate that modulation effects displayed by lipocalins through this sequence motif involve cell survival, extracellular matrix remodeling, and cytokine signaling.Such effects can be related to the lipocalin roles in disease, development, and tissue repair.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Biochemistry and Biophysics, Butantan Institute, Avenida Vital Brasil 1500, 05503-900 São Paulo, SP, Brazil.

ABSTRACT
Lipocalin family members have been implicated in development, regeneration, and pathological processes, but their roles are unclear. Interestingly, these proteins are found abundant in the venom of the Lonomia obliqua caterpillar. Lipocalins are β-barrel proteins, which have three conserved motifs in their amino acid sequence. One of these motifs was shown to be a sequence signature involved in cell modulation. The aim of this study is to investigate the effects of a synthetic peptide comprising the lipocalin sequence motif in fibroblasts. This peptide suppressed caspase 3 activity and upregulated Bcl-2 and Ki-67, but did not interfere with GPCR calcium mobilization. Fibroblast responses also involved increased expression of proinflammatory mediators. Increase of extracellular matrix proteins, such as collagen, fibronectin, and tenascin, was observed. Increase in collagen content was also observed in vivo. Results indicate that modulation effects displayed by lipocalins through this sequence motif involve cell survival, extracellular matrix remodeling, and cytokine signaling. Such effects can be related to the lipocalin roles in disease, development, and tissue repair.

No MeSH data available.


Related in: MedlinePlus