Scleroderma-like Impairment in the Network of Telocytes/CD34<sup>+</sup> Stromal Cells in the Experimental Mouse Model of Bleomycin-Induced Dermal Fibrosis

Considerable evidence accumulated over the past decade supports that telocytes (TCs)/CD34<sup>+</sup> stromal cells represent an exclusive type of interstitial cells identifiable by transmission electron microscopy (TEM) or immunohistochemistry in various organs of the human body, includ...

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Auteurs principaux:	Irene Rosa, Eloisa Romano, Bianca Saveria Fioretto, Daniele Guasti, Lidia Ibba-Manneschi, Marco Matucci-Cerinic, Mirko Manetti
Format:	article
Langue:	EN
Publié:	MDPI AG 2021
Sujets:	dermal fibrosis mouse model scleroderma skin systemic sclerosis telocytes/CD34<sup>+</sup> stromal cells Biology (General) QH301-705.5 Chemistry QD1-999
Accès en ligne:	https://doaj.org/article/b16862264a8f4d25b7ee27c6db46c159
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spelling	oai:doaj.org-article:b16862264a8f4d25b7ee27c6db46c1592021-11-25T17:56:22ZScleroderma-like Impairment in the Network of Telocytes/CD34<sup>+</sup> Stromal Cells in the Experimental Mouse Model of Bleomycin-Induced Dermal Fibrosis10.3390/ijms2222124071422-00671661-6596https://doaj.org/article/b16862264a8f4d25b7ee27c6db46c1592021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12407https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Considerable evidence accumulated over the past decade supports that telocytes (TCs)/CD34<sup>+</sup> stromal cells represent an exclusive type of interstitial cells identifiable by transmission electron microscopy (TEM) or immunohistochemistry in various organs of the human body, including the skin. By means of their characteristic cellular extensions (telopodes), dermal TCs are arranged in networks intermingled with a multitude of neighboring cells and, hence, they are thought to contribute to skin homeostasis through both intercellular contacts and releasing extracellular vesicles. In this context, fibrotic skin lesions from patients with systemic sclerosis (SSc, scleroderma) appear to be characterized by a disruption of the dermal network of TCs, which has been ascribed to either cell degenerative processes or possible transformation into profibrotic myofibroblasts. In the present study, we utilized the well-established mouse model of bleomycin-induced scleroderma to gain further insights into the TC alterations found in cutaneous fibrosis. CD34 immunofluorescence revealed a severe impairment in the dermal network of TCs/CD34<sup>+</sup> stromal cells in bleomycin-treated mice. CD31/CD34 double immunofluorescence confirmed that CD31<sup>−</sup>/CD34<sup>+</sup> TC counts were greatly reduced in the skin of bleomycin-treated mice compared with control mice. Ultrastructural signs of TC injury were detected in the skin of bleomycin-treated mice by TEM. The analyses of skin samples from mice treated with bleomycin for different times by either TEM or double immunostaining and immunoblotting for the CD34/α-SMA antigens collectively suggested that, although a few TCs may transition to α-SMA<sup>+</sup> myofibroblasts in the early disease stage, most of these cells rather undergo degeneration, and then are lost. Taken together, our data demonstrate that TC changes in the skin of bleomycin-treated mice mimic very closely those observed in human SSc skin, which makes this experimental model a suitable tool to (i) unravel the pathological mechanisms underlying TC damage and (ii) clarify the possible contribution of the TC loss to the development/progression of dermal fibrosis. In perspective, these findings may have important implications in the field of skin regenerative medicine.Irene RosaEloisa RomanoBianca Saveria FiorettoDaniele GuastiLidia Ibba-ManneschiMarco Matucci-CerinicMirko ManettiMDPI AGarticledermal fibrosismouse modelsclerodermaskinsystemic sclerosistelocytes/CD34<sup>+</sup> stromal cellsBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12407, p 12407 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	dermal fibrosis mouse model scleroderma skin systemic sclerosis telocytes/CD34<sup>+</sup> stromal cells Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	dermal fibrosis mouse model scleroderma skin systemic sclerosis telocytes/CD34<sup>+</sup> stromal cells Biology (General) QH301-705.5 Chemistry QD1-999 Irene Rosa Eloisa Romano Bianca Saveria Fioretto Daniele Guasti Lidia Ibba-Manneschi Marco Matucci-Cerinic Mirko Manetti Scleroderma-like Impairment in the Network of Telocytes/CD34<sup>+</sup> Stromal Cells in the Experimental Mouse Model of Bleomycin-Induced Dermal Fibrosis
description	Considerable evidence accumulated over the past decade supports that telocytes (TCs)/CD34<sup>+</sup> stromal cells represent an exclusive type of interstitial cells identifiable by transmission electron microscopy (TEM) or immunohistochemistry in various organs of the human body, including the skin. By means of their characteristic cellular extensions (telopodes), dermal TCs are arranged in networks intermingled with a multitude of neighboring cells and, hence, they are thought to contribute to skin homeostasis through both intercellular contacts and releasing extracellular vesicles. In this context, fibrotic skin lesions from patients with systemic sclerosis (SSc, scleroderma) appear to be characterized by a disruption of the dermal network of TCs, which has been ascribed to either cell degenerative processes or possible transformation into profibrotic myofibroblasts. In the present study, we utilized the well-established mouse model of bleomycin-induced scleroderma to gain further insights into the TC alterations found in cutaneous fibrosis. CD34 immunofluorescence revealed a severe impairment in the dermal network of TCs/CD34<sup>+</sup> stromal cells in bleomycin-treated mice. CD31/CD34 double immunofluorescence confirmed that CD31<sup>−</sup>/CD34<sup>+</sup> TC counts were greatly reduced in the skin of bleomycin-treated mice compared with control mice. Ultrastructural signs of TC injury were detected in the skin of bleomycin-treated mice by TEM. The analyses of skin samples from mice treated with bleomycin for different times by either TEM or double immunostaining and immunoblotting for the CD34/α-SMA antigens collectively suggested that, although a few TCs may transition to α-SMA<sup>+</sup> myofibroblasts in the early disease stage, most of these cells rather undergo degeneration, and then are lost. Taken together, our data demonstrate that TC changes in the skin of bleomycin-treated mice mimic very closely those observed in human SSc skin, which makes this experimental model a suitable tool to (i) unravel the pathological mechanisms underlying TC damage and (ii) clarify the possible contribution of the TC loss to the development/progression of dermal fibrosis. In perspective, these findings may have important implications in the field of skin regenerative medicine.
format	article
author	Irene Rosa Eloisa Romano Bianca Saveria Fioretto Daniele Guasti Lidia Ibba-Manneschi Marco Matucci-Cerinic Mirko Manetti
author_facet	Irene Rosa Eloisa Romano Bianca Saveria Fioretto Daniele Guasti Lidia Ibba-Manneschi Marco Matucci-Cerinic Mirko Manetti
author_sort	Irene Rosa
title	Scleroderma-like Impairment in the Network of Telocytes/CD34<sup>+</sup> Stromal Cells in the Experimental Mouse Model of Bleomycin-Induced Dermal Fibrosis
title_short	Scleroderma-like Impairment in the Network of Telocytes/CD34<sup>+</sup> Stromal Cells in the Experimental Mouse Model of Bleomycin-Induced Dermal Fibrosis
title_full	Scleroderma-like Impairment in the Network of Telocytes/CD34<sup>+</sup> Stromal Cells in the Experimental Mouse Model of Bleomycin-Induced Dermal Fibrosis
title_fullStr	Scleroderma-like Impairment in the Network of Telocytes/CD34<sup>+</sup> Stromal Cells in the Experimental Mouse Model of Bleomycin-Induced Dermal Fibrosis
title_full_unstemmed	Scleroderma-like Impairment in the Network of Telocytes/CD34<sup>+</sup> Stromal Cells in the Experimental Mouse Model of Bleomycin-Induced Dermal Fibrosis
title_sort	scleroderma-like impairment in the network of telocytes/cd34<sup>+</sup> stromal cells in the experimental mouse model of bleomycin-induced dermal fibrosis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/b16862264a8f4d25b7ee27c6db46c159
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Scleroderma-like Impairment in the Network of Telocytes/CD34<sup>+</sup> Stromal Cells in the Experimental Mouse Model of Bleomycin-Induced Dermal Fibrosis

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