Transforming growth factor-β (TGF-β) signaling in healthy human fetal skin: A descriptive study

Walraven, Maudy; Beelen, Robert H.J.; Ulrich, Magda M. W.

doi:10.1016/j.jdermsci.2015.02.012

Cited by 24 publications

(18 citation statements)

References 28 publications

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“…This suggests that changes in other PGs are responsible for the intrinsically aged skin phenotype. While the mRNA level of biglycan was similar between fetal and adult skin [4], intrinsic aging or photoaging-related changes in biglycan have not been reported. Thus we examined aging-related changes in biglycan by immunostaining (1:50, AF2667, R&D Systems, Minneapolis, MN, USA) in young and old buttock skin and forearm skin (Fig.…”

Section: Changes In Sulfated Gags and Pgsmentioning

confidence: 80%

“…However, others reported that versican expression in adult skin was reduced compared to that in fetal skin, and decorin expression levels showed no differences but showed reduced molecular weight and additional cleavage products in adult skin [19,32], while the mRNA level of decorin was found to be elevated in adult skin [4]. Recently, Li et al demonstrated that the GAG chain of decorin was reduced in intrinsically aged skin [20].…”

Section: Changes In Sulfated Gags and Pgsmentioning

confidence: 99%

“…MMP-1 is known as an initiator collagenase responsible for collagen fragmentation in skin aging process, and MMP-2 and -9 are known to be responsible for further degradation of collagen [1,3]. Impaired TGF-β signalingcaused reduction of collagen synthesis is another reason for collagen loss in aged skin [2,4]. However, various strategies focusing on collagen turnover remain unsatisfactory for the reversal or prevention of skin aging.…”

Section: Introductionmentioning

confidence: 99%

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Glycosaminoglycan and proteoglycan in skin aging

Lee

Chung

2016

Journal of Dermatological Science

157

151

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Section: Changes In Sulfated Gags and Pgsmentioning

confidence: 80%

Section: Changes In Sulfated Gags and Pgsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Glycosaminoglycan and proteoglycan in skin aging

Lee

Chung

2016

Journal of Dermatological Science

157

151

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“…This may explain the difference in the subcellular localization of pSmad2/3 between the col7a1 −/− mouse skin and acutely wounded skin. Indeed, cytoplasmic localization of pSmad2/3 was observed in subtypes of human trophoblast, as well as healthy human fetal skin [40,41]. The implication of the cytoplasmic localization of pSmad2/3 in the pathological development of RDEB skin requires further investigation.…”

Section: Discussionmentioning

confidence: 97%

Cord Blood-Derived Stem Cells Suppress Fibrosis and May Prevent Malignant Progression in Recessive Dystrophic Epidermolysis Bullosa

et al. 2018

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Recessive dystrophic epidermolysis bullosa (RDEB) is a severe skin fragility disorder caused by mutations in the Col7a1 gene. Patients with RDEB suffer from recurrent erosions in skin and mucous membranes and have a high risk for developing cutaneous squamous cell carcinoma (cSCCs). TGFβ signaling has been associated with fibrosis and malignancy in RDEB. In this study, the activation of TGFβ signaling was demonstrated in col7a1−/− mice as early as a week after birth starting in the interdigital folds of the paws, accompanied by increased deposition of collagen fibrils and elevated dermal expression of matrix metalloproteinase (MMP)‐9 and MMP‐13. Furthermore, human cord blood‐derived unrestricted somatic stem cells (USSCs) that we previously demonstrated to significantly improve wound healing and prolong the survival of col7a1−/− mice showed the ability to suppress TGFβ signaling and MMP‐9 and MMP‐13 expression meanwhile upregulating anti‐fibrotic TGFβ3 and decorin. In parallel, we cocultured USSCs in a transwell with RDEB patient‐derived fibroblasts, keratinocytes, and cSCC, respectively. The patient‐derived cells were constitutively active for STAT, but not TGFβ signaling. Moreover, the levels of MMP‐9 and MMP‐13 were significantly elevated in the patient derived‐keratinocytes and cSCCs. Although USSC coculture did not inhibit STAT signaling, it significantly suppressed the secretion of MMP‐9 and MMP‐13, and interferon (IFN)‐γ from RDEB patient‐derived cells. Since epithelial expression of these MMPs is a biomarker of malignant transformation and correlates with the degree of tumor invasion, these results suggest a potential role for USSCs in mitigating epithelial malignancy, in addition to their anti‐inflammatory and anti‐fibrotic functions. Stem Cells 2018;36:1839–12

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“…Luminex samples were prepared as was previously described . In short, frozen skin samples were lysed and homogenized in MILLIPLEX MAP Lysis Buffer (Millipore, Billerica, MA).…”

Section: Methodsmentioning

confidence: 99%

Healthy human second‐trimester fetal skin is deficient in leukocytes and associated homing chemokines

Walraven

Talhout

Beelen

et al. 2016

Wound Repair Regeneration

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The lack of immune cells in mid-gestational fetal skin is often mentioned as a key factor underlying scarless healing. However, the scarless healing ability is conserved until long after the immune system in the fetus is fully developed. Therefore, we studied human second-trimester fetal skin and compared the numbers of immune cells and chemokine levels from fetal skin with adult skin. By using immunohistochemistry, we show that healthy fetal skin contains significant lower numbers of CD68(+) -macrophages, Tryptase(+) -mast cells, Langerin(+) -Langerhans cells, CD1a(+) -dendritic cells, and CD3(+) -T cells compared to adult skin. Staining with an early lineage leukocyte marker, i.e., CD45, verified that the number of CD45(+) -immune cells was indeed significantly lower in fetal skin but that sufficient numbers of immune cells were present in the fetal lymph node. No differences in the vascular network were observed between fetal and adult skin. Moreover, significant lower levels of lymphocyte chemokines CCL17, CCL21, and CCL27 were observed in fetal skin. However, levels of inflammatory interleukins such as IL-6, IL-8, and IL-10 were undetectable and levels of CCL2 were similar in healthy fetal and adult skin. In conclusion, this study shows that second-trimester fetal skin contains low levels of immune cells and leukocyte chemokines compared to adult skin. This immune cell deficiency includes CD45(+) leukocytes, despite the abundant presence of these cells in the lymph node. The immune deficiency in healthy second-trimester fetal skin may result in reduced inflammation during wound healing, and could underlie the scarless healing capacities of the fetal skin.

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Transforming growth factor-β (TGF-β) signaling in healthy human fetal skin: A descriptive study

Cited by 24 publications

References 28 publications

Glycosaminoglycan and proteoglycan in skin aging

Glycosaminoglycan and proteoglycan in skin aging

Cord Blood-Derived Stem Cells Suppress Fibrosis and May Prevent Malignant Progression in Recessive Dystrophic Epidermolysis Bullosa

Healthy human second‐trimester fetal skin is deficient in leukocytes and associated homing chemokines

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