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Connective tissue growth factor is induced in bleomycin-induced skin scleroderma.

Liu S, Taghavi R, Leask A - J Cell Commun Signal (2009)

Bottom Line: Approximately 85% of myofibroblasts were NG2-positive, CCN2-expressing pericytes, indicating that pericytes significantly contributed to the presence of myofibroblasts in sclerotic dermis.Thus CCN2 is induced in fibrotic skin, correlating with the induction of myofibroblast induction.Moreover, CCN2-expressing pericytes significantly contribute to the appearance of myofibroblasts in bleomycin-induced skin scleroderma.

View Article: PubMed Central - PubMed

Affiliation: CIHR Group in Skeletal Development and Remodeling, Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Dental Sciences Building, University of Western Ontario, London, ON N6A 5C1 Canada.

ABSTRACT
The origin of fibrotic cells within connective tissue is unclear. For example, the extent to which microvascular pericytes contribute to the number of myofibroblasts present in dermal fibrosis in uncertain. Connective tissue growth factor (CTGF/CCN2) is a marker and mediator of fibrosis. In this report, we use an antibody recognizing CCN2 to assess the cell types in mouse dermis which express CCN2 in the bleomycin model of skin scleroderma. Control (PBS injected) and fibrotic (bleomycin-injected) dermis was examined for CCN2, alpha-smooth muscle actin (alpha-SMA) (to detect myofibroblasts), and NG2 (to detect pericytes) expression. Consistent with previously published data, CCN2 expression was largely absent in the dermis of control mice. However, upon exposure to bleomycin, CCN2 was observed in the dermis. Cells that expressed CCN2 were alpha-SMA-expressing myofibroblasts. Approximately 85% of myofibroblasts were NG2-positive, CCN2-expressing pericytes, indicating that pericytes significantly contributed to the presence of myofibroblasts in sclerotic dermis. Thus CCN2 is induced in fibrotic skin, correlating with the induction of myofibroblast induction. Moreover, CCN2-expressing pericytes significantly contribute to the appearance of myofibroblasts in bleomycin-induced skin scleroderma.

No MeSH data available.


Related in: MedlinePlus

CCN2 promoter is expressed in myofibroblasts in response to bleomycin. Skin of mice treated with PBS or bleomycin was fixed, sectioned, and stained with DAPI to detect nuclei, anti-α-SMA antibody to detect myofibroblasts and anti-CCN2 promoter antibody (10× magnification of dermal tissue). The percentage of fibroblasts within the wound that were α−SMA positive, CCN2- positive, and CCN2/α-SMA positive was calculated as described in Methods. Representative data from n = 4 wounds from 4 separate animals are shown
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Fig1: CCN2 promoter is expressed in myofibroblasts in response to bleomycin. Skin of mice treated with PBS or bleomycin was fixed, sectioned, and stained with DAPI to detect nuclei, anti-α-SMA antibody to detect myofibroblasts and anti-CCN2 promoter antibody (10× magnification of dermal tissue). The percentage of fibroblasts within the wound that were α−SMA positive, CCN2- positive, and CCN2/α-SMA positive was calculated as described in Methods. Representative data from n = 4 wounds from 4 separate animals are shown

Mentions: The cell types expressing CCN2 in fibrosis are unclear. To address this issue, C57/BL6 mice were subjected to subcutaneous injections of PBS or bleomycin over 28 days. As we were interested in the expression of CCN2 in connective tissue and in the origin of myofibroblasts within connective tissue, we focused our studies specifically on the dermis. When control PBS-injected skin was examined, a few CCN2-positive cells were detected in the dermis (Fig. 1, CCN2, PBS). Conversely, in response to bleomycin, CCN2 expression was strongly induced in the dermis (Fig. 1, CCN2, bleo). Similar patterns of expression were observed when tissue sections were stained with anti-α-SMA antibody to detect the presence of myofibroblasts (Fig. 1, α-SMA). Cells expressing CCN2 were also α−SMA positive (Fig. 1, merge). Collectively, these data indicate that CCN2 is expressed in myofibroblasts in response to bleomycin.Fig. 1


Connective tissue growth factor is induced in bleomycin-induced skin scleroderma.

Liu S, Taghavi R, Leask A - J Cell Commun Signal (2009)

CCN2 promoter is expressed in myofibroblasts in response to bleomycin. Skin of mice treated with PBS or bleomycin was fixed, sectioned, and stained with DAPI to detect nuclei, anti-α-SMA antibody to detect myofibroblasts and anti-CCN2 promoter antibody (10× magnification of dermal tissue). The percentage of fibroblasts within the wound that were α−SMA positive, CCN2- positive, and CCN2/α-SMA positive was calculated as described in Methods. Representative data from n = 4 wounds from 4 separate animals are shown
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2821481&req=5

Fig1: CCN2 promoter is expressed in myofibroblasts in response to bleomycin. Skin of mice treated with PBS or bleomycin was fixed, sectioned, and stained with DAPI to detect nuclei, anti-α-SMA antibody to detect myofibroblasts and anti-CCN2 promoter antibody (10× magnification of dermal tissue). The percentage of fibroblasts within the wound that were α−SMA positive, CCN2- positive, and CCN2/α-SMA positive was calculated as described in Methods. Representative data from n = 4 wounds from 4 separate animals are shown
Mentions: The cell types expressing CCN2 in fibrosis are unclear. To address this issue, C57/BL6 mice were subjected to subcutaneous injections of PBS or bleomycin over 28 days. As we were interested in the expression of CCN2 in connective tissue and in the origin of myofibroblasts within connective tissue, we focused our studies specifically on the dermis. When control PBS-injected skin was examined, a few CCN2-positive cells were detected in the dermis (Fig. 1, CCN2, PBS). Conversely, in response to bleomycin, CCN2 expression was strongly induced in the dermis (Fig. 1, CCN2, bleo). Similar patterns of expression were observed when tissue sections were stained with anti-α-SMA antibody to detect the presence of myofibroblasts (Fig. 1, α-SMA). Cells expressing CCN2 were also α−SMA positive (Fig. 1, merge). Collectively, these data indicate that CCN2 is expressed in myofibroblasts in response to bleomycin.Fig. 1

Bottom Line: Approximately 85% of myofibroblasts were NG2-positive, CCN2-expressing pericytes, indicating that pericytes significantly contributed to the presence of myofibroblasts in sclerotic dermis.Thus CCN2 is induced in fibrotic skin, correlating with the induction of myofibroblast induction.Moreover, CCN2-expressing pericytes significantly contribute to the appearance of myofibroblasts in bleomycin-induced skin scleroderma.

View Article: PubMed Central - PubMed

Affiliation: CIHR Group in Skeletal Development and Remodeling, Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Dental Sciences Building, University of Western Ontario, London, ON N6A 5C1 Canada.

ABSTRACT
The origin of fibrotic cells within connective tissue is unclear. For example, the extent to which microvascular pericytes contribute to the number of myofibroblasts present in dermal fibrosis in uncertain. Connective tissue growth factor (CTGF/CCN2) is a marker and mediator of fibrosis. In this report, we use an antibody recognizing CCN2 to assess the cell types in mouse dermis which express CCN2 in the bleomycin model of skin scleroderma. Control (PBS injected) and fibrotic (bleomycin-injected) dermis was examined for CCN2, alpha-smooth muscle actin (alpha-SMA) (to detect myofibroblasts), and NG2 (to detect pericytes) expression. Consistent with previously published data, CCN2 expression was largely absent in the dermis of control mice. However, upon exposure to bleomycin, CCN2 was observed in the dermis. Cells that expressed CCN2 were alpha-SMA-expressing myofibroblasts. Approximately 85% of myofibroblasts were NG2-positive, CCN2-expressing pericytes, indicating that pericytes significantly contributed to the presence of myofibroblasts in sclerotic dermis. Thus CCN2 is induced in fibrotic skin, correlating with the induction of myofibroblast induction. Moreover, CCN2-expressing pericytes significantly contribute to the appearance of myofibroblasts in bleomycin-induced skin scleroderma.

No MeSH data available.


Related in: MedlinePlus