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Investigation of sensory neurogenic components in a bleomycin-induced scleroderma model using transient receptor potential vanilloid 1 receptor- and calcitonin gene-related peptide-knockout mice.
Arthritis Rheum. 2008 Jan; 58(1):292-301.AR

Abstract

OBJECTIVE

Along with their classic afferent function (nociception), capsaicin-sensitive transient receptor potential vanilloid 1 (TRPV1) receptor-expressing sensory nerve terminals exert local and systemic efferent activities. Activation of TRPV1 causes sensory neuropeptide release, which modulates the inflammation process. The aim of the present study was to examine the role of this modulatory role of TRPV1 receptor and that of calcitonin gene-related peptide (CGRP) in bleomycin-induced scleroderma, using transgenic mice.

METHODS

Cutaneous sclerosis was induced with daily subcutaneous injections of bleomycin for 30 days. Control groups were treated with phosphate buffered saline (PBS). TRPV1 receptor gene-deficient (TRPV1(-/-)) mice and CGRP-knockout (CGRP(-/-)) mice and their wild-type (WT) counterparts were investigated. A composite sclerosis score was calculated on the basis of thickening, leukocyte infiltration, and the amount/orientation of collagen bundles. Dermal thickness and the number of alpha-smooth muscle actin (alpha-SMA)-positive cells were also determined. The quantity of the collagen-specific amino acid hydroxyproline was measured by spectrophotometry.

RESULTS

Bleomycin treatment induced marked cutaneous thickening and fibrosis compared with that observed in control mice treated with PBS. The composite sclerosis score was 18% higher, dermal thickness was 19% higher, the number of alpha-SMA-positive cells was 47% higher, and the amount of hydroxyproline was 57% higher in TRPV1(-/-) mice than in their WT counterparts. Similarly, the composite sclerosis score was 47% higher, dermal thickness was 29% higher, the number of alpha-SMA-positive cells was 76% higher, and the amount of hydroxyproline was 30% higher in CGRP(-/-) mice than in the respective WT groups.

CONCLUSION

These results suggest that activation of the TRPV1 receptor by mediators of inflammation induces sensory neuropeptide release, which might exert protective action against fibrosis. We confirmed the protective role of CGRP in the development of cutaneous sclerosis.

Authors+Show Affiliations

University of Pécs, Pécs, Hungary.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18163477

Citation

Szabó, Arpád, et al. "Investigation of Sensory Neurogenic Components in a Bleomycin-induced Scleroderma Model Using Transient Receptor Potential Vanilloid 1 Receptor- and Calcitonin Gene-related Peptide-knockout Mice." Arthritis and Rheumatism, vol. 58, no. 1, 2008, pp. 292-301.
Szabó A, Czirják L, Sándor Z, et al. Investigation of sensory neurogenic components in a bleomycin-induced scleroderma model using transient receptor potential vanilloid 1 receptor- and calcitonin gene-related peptide-knockout mice. Arthritis Rheum. 2008;58(1):292-301.
Szabó, A., Czirják, L., Sándor, Z., Helyes, Z., László, T., Elekes, K., Czömpöly, T., Starr, A., Brain, S., Szolcsányi, J., & Pintér, E. (2008). Investigation of sensory neurogenic components in a bleomycin-induced scleroderma model using transient receptor potential vanilloid 1 receptor- and calcitonin gene-related peptide-knockout mice. Arthritis and Rheumatism, 58(1), 292-301. https://doi.org/10.1002/art.23168
Szabó A, et al. Investigation of Sensory Neurogenic Components in a Bleomycin-induced Scleroderma Model Using Transient Receptor Potential Vanilloid 1 Receptor- and Calcitonin Gene-related Peptide-knockout Mice. Arthritis Rheum. 2008;58(1):292-301. PubMed PMID: 18163477.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Investigation of sensory neurogenic components in a bleomycin-induced scleroderma model using transient receptor potential vanilloid 1 receptor- and calcitonin gene-related peptide-knockout mice. AU - Szabó,Arpád, AU - Czirják,László, AU - Sándor,Zoltán, AU - Helyes,Zsuzsanna, AU - László,Terézia, AU - Elekes,Krisztián, AU - Czömpöly,Tamás, AU - Starr,Anna, AU - Brain,Susan, AU - Szolcsányi,János, AU - Pintér,Erika, PY - 2008/1/1/pubmed PY - 2008/3/11/medline PY - 2008/1/1/entrez SP - 292 EP - 301 JF - Arthritis and rheumatism JO - Arthritis Rheum VL - 58 IS - 1 N2 - OBJECTIVE: Along with their classic afferent function (nociception), capsaicin-sensitive transient receptor potential vanilloid 1 (TRPV1) receptor-expressing sensory nerve terminals exert local and systemic efferent activities. Activation of TRPV1 causes sensory neuropeptide release, which modulates the inflammation process. The aim of the present study was to examine the role of this modulatory role of TRPV1 receptor and that of calcitonin gene-related peptide (CGRP) in bleomycin-induced scleroderma, using transgenic mice. METHODS: Cutaneous sclerosis was induced with daily subcutaneous injections of bleomycin for 30 days. Control groups were treated with phosphate buffered saline (PBS). TRPV1 receptor gene-deficient (TRPV1(-/-)) mice and CGRP-knockout (CGRP(-/-)) mice and their wild-type (WT) counterparts were investigated. A composite sclerosis score was calculated on the basis of thickening, leukocyte infiltration, and the amount/orientation of collagen bundles. Dermal thickness and the number of alpha-smooth muscle actin (alpha-SMA)-positive cells were also determined. The quantity of the collagen-specific amino acid hydroxyproline was measured by spectrophotometry. RESULTS: Bleomycin treatment induced marked cutaneous thickening and fibrosis compared with that observed in control mice treated with PBS. The composite sclerosis score was 18% higher, dermal thickness was 19% higher, the number of alpha-SMA-positive cells was 47% higher, and the amount of hydroxyproline was 57% higher in TRPV1(-/-) mice than in their WT counterparts. Similarly, the composite sclerosis score was 47% higher, dermal thickness was 29% higher, the number of alpha-SMA-positive cells was 76% higher, and the amount of hydroxyproline was 30% higher in CGRP(-/-) mice than in the respective WT groups. CONCLUSION: These results suggest that activation of the TRPV1 receptor by mediators of inflammation induces sensory neuropeptide release, which might exert protective action against fibrosis. We confirmed the protective role of CGRP in the development of cutaneous sclerosis. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/18163477/Investigation_of_sensory_neurogenic_components_in_a_bleomycin_induced_scleroderma_model_using_transient_receptor_potential_vanilloid_1_receptor__and_calcitonin_gene_related_peptide_knockout_mice_ L2 - https://doi.org/10.1002/art.23168 DB - PRIME DP - Unbound Medicine ER -