BMP-7 suppresses excessive scar formation by activating the BMP-7/Smad1/5/8 signaling pathway

Guo, Jingdong; Lin, Qi; Shao, Ying; Li, Rong; Zhang, Duo

doi:10.3892/mmr.2017.6779

Cited by 29 publications

(29 citation statements)

References 28 publications

(27 reference statements)

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“…BMP7 is a member of TGFβsuperfamily and has been veri ed to reduce brosis in various tissues [16][17][18][19][20][21][22][23][24][25][47][48][49]. Previous clinical observations indicated that BMP-7 can suppress brosis in renal and myocardial through reducing epithelial-mesenchymal transition and counteracting TGF-β1 signaling pathway [21,22].…”

Section: Discussionmentioning

confidence: 99%

“…Fractional CO2 laser(FCO2L) and 595-nm pulsed dye laser (PDL) are selective phototherapeutics, and have been validated to be effective in therapy of HS [9][10][11][12][13][14], yet their underlying mechanisms remain unclear, and need validation through measurement of bone morphogenetic protein-7(BMP-7) and Fas gene, the two important proteins that affect the prognosis of this condition on molecular study basis. BMP-7, a TGF-β superfamily, has been shown to effectively inhibit the brosis process through regulating cell proliferation, differentiation and apoptosis in various organs and tissuesin series of studies [15][16][17][18][19][20][21][22][23][24][25]. Jin Y [22] found that BMP-7 can undermine TGF-β1 signaling pathway and reduce myocardial brosis to protect the heart, and more reports described that BMP-7 was involved in the development of hypertrophic scars after wound healing and capable of inhibiting the transformation of rat hair mastoid cells (DPCs) into broblasts [16,17,20,21,24,25].…”

Section: Introductionmentioning

confidence: 99%

“…BMP-7, a TGF-β superfamily, has been shown to effectively inhibit the brosis process through regulating cell proliferation, differentiation and apoptosis in various organs and tissuesin series of studies [15][16][17][18][19][20][21][22][23][24][25]. Jin Y [22] found that BMP-7 can undermine TGF-β1 signaling pathway and reduce myocardial brosis to protect the heart, and more reports described that BMP-7 was involved in the development of hypertrophic scars after wound healing and capable of inhibiting the transformation of rat hair mastoid cells (DPCs) into broblasts [16,17,20,21,24,25]. Still, further studies revealed that BMP-7 can produce inhibitory effects on excessive scar formation by activating BMP-7/Smad1/5/8 signaling pathway in broblasts to interfere with the cellular functions and reduce cell proliferation in HSs via inhibiting the BMP-7 related signaling pathway [19,24,25].…”

Section: Introductionmentioning

confidence: 99%

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Fractional CO2 laser combined with 595-nm PDL inhibiting hypertrophic scars via measuring BMP-7 and Fas expression in rabbit models

Zhang¹,

Zhou²,

Xia³

et al. 2020

Preprint

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Background and ObjectivesAlthough the treatment of hypertrophic scar (HS) remain challenging, fractional CO2 laser (FCO2L) and 595-nm pulsed-dye laser (PDL) have proved clinical efficacy. Meanwhile, BMP-7 and Fas proteins are demonstrated to promote wound healing and inhibit scar formation, yet few reports on the effect of the two proteins on hypertrophic scarring are available, and their molecular mechanisms remain unclear. In current study, we attempted to observe the effect of combined use of FCO2L with 595-nm PDL in HS animal models through determining the expression of BMP-7 and Fas in scar inhibition.Materials and MethodsTwenty New Zealand white rabbits were randomized to control group, FCO2L group, PDL group and combined treatment group. Four HS samples were developed at each ear of individual rabbit. FCO2L was respectively applied to simple FCO2L and combined treatment group, and simple 595-nm PDL and combined treatment group. Totally, 3 sessions of treatments were carried out once every 14 days. Then, the changes of fibroblasts and collagens in HSs and expression of BMP-7 and Fas proteins in the scar tissues were determined via histological and immunohistochemical studies, ELISA, CCK8 test, RT-PCR and Western blot assay.ResultsHSs were flattened and shrunk after treatment, especially in rabbits treated by FCO2L plus 595-nm PDL group, in which obviously decreased abnormal fibroblast and collagen were noted. The deference was significant compared to other groups(P < 0.001). Moreover, expression of BMP-7 and Fas was both increased in the combined treatment group compared to single FCO2L or 595-nm PDL therapy group (P < 0.001) .ConclusionsFCO2L combined with 595-nm PDL can improve HSs in rabbit models by inhibiting excessive fibroblast growth and collagen deposition. This may be associated with increased BMP-7 and Fas expression in the scar tissues. And our findings may pioneer a new therapeutic strategy for alternative treatment of HSs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Fractional CO2 laser combined with 595-nm PDL inhibiting hypertrophic scars via measuring BMP-7 and Fas expression in rabbit models

Zhang¹,

Zhou²,

Xia³

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…Moreover, it is also very important in the occurrence and development of acute and chronic lung injury (21). It has been found that TGF-β1, interleukin 8 (IL-8) and staphylococcal protein A (SPA) are highly expressed in pulmonary lavage fluid of BDP children (22). TGF-β1 can not only promote the process of pulmonary fibrosis, but also induce the high expression of connective tissue growth factor (CTGF) in lung, thereby promoting the development of pulmonary fibrosis (23).…”

Section: Discussionmentioning

confidence: 99%

Correlation between serum transforming growth factor β1, interleukin‑6 and neonatal respiratory distress syndrome

2019

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Trend and correlation of transforming growth factor β1 (TGF-β1) and interleukin-6 (IL-6) in serum of children with neonatal respiratory distress syndrome (NRDS) were investigated. A total of 75 NRDS children born in the Xiangyang Central Hospital from July 2015 to August 2017 were analyzed retrospectively. A total of 45 NRDS premature infants who received pulmonary surfactant (PS) within 12 h after birth were treated as PS group, 30 who did not receive PS treatment as non-PS group, and 32 premature infants without NRDS in the same period were selected as control group. Serum levels of TGF-β1 and IL-6 were detected by enzyme linked immunosorbent assay (ELISA) at various time points after birth and their correlation was analyzed. The expression level of TGF-β1 in serum of children in PS group was significantly higher than that in control group on days 1 and 3 after birth (P<0.05). The expression level of TGF-β1 in non-PS group increased continuously with the increase of number of days and was significantly higher than that in control group on days 1, 3 and 7 after birth (P<0.05), and significantly higher than that in PS group on days 3 and 7 after birth (P<0.05). The analysis of the correlation between the severity of the disease and the expression levels of TGF-β1 and IL-6 showed that the expression levels were elevated with the increase of the disease severity. The expression levels of TGF-β1 and IL-6 were positively correlated with severity of the disease (r=0.7509, P<0.05; r=0.8056, P<0.05). The expression levels of TGF-β1 and IL-6 in PS and non-PS groups were positively correlated (r=0.9042, P<0.05; r=0.8905, P<0.05). The results showed that serum TGF-β1 and IL-6 were elevated in NRDS children, and there was a positive correlation between them.

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“…In a Schistosoma japonicum -infected liver fibrosis model, BMP7 regulated liver fibrosis through the TGF-β-Smad signaling pathway[10]. During the development of liver fibrosis, BMP7 activated Smad1/5/8 to inhibit fibrosis[11,12]. In addition, BMP7 inhibited ColIa1 expression by increasing MMP13 and decreasing TIMP2 expression to further inhibit fibrosis[13].…”

Section: Introductionmentioning

confidence: 99%

Bone morphogenetic protein-7 represses hepatic stellate cell activation and liver fibrosis via regulation of TGF-β/Smad signaling pathway

Zou

Zuo

Lü

et al. 2019

WJG

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BACKGROUND Liver fibrosis is a refractory disease whose persistence can eventually induce cirrhosis or even liver cancer. Early liver fibrosis is reversible by intervention. As a member of the transforming growth factor-beta (TGF-β) superfamily, bone morphogenetic protein 7 (BMP7) has anti-liver fibrosis functions. However, little is known about BMP7 expression changes and its potential regulatory mechanism as well as the relationship between BMP7 and TGF-β during liver fibrosis. In addition, the mechanism underlying the anti-liver fibrosis function of BMP7 needs to be further explored. AIM To investigate changes in the dynamic expression of BMP7 during liver fibrosis, interactions between BMP7 and TGF-β1, and possible mechanisms underlying the anti-liver fibrosis function of BMP7. METHODS Changes in BMP7 expression during liver fibrosis and the interaction between BMP7 and TGF-β1 in mice were observed. Exogenous BMP7 was used to treat mouse primary hepatic stellate cells (HSCs) to observe its effect on activation, migration, and proliferation of HSCs and explore the possible mechanism underlying the anti-liver fibrosis function of BMP7. Mice with liver fibrosis received exogenous BMP7 intervention to observe improvement of liver fibrosis by using Masson’s trichrome staining and detecting the expression of the HSC activation indicator alpha-smooth muscle actin (α-SMA) and the collagen formation associated protein type I collagen (Col I). Changes in the dynamic expression of BMP7 during liver fibrosis in the human body were further observed. RESULTS In the process of liver fibrosis induced by carbon tetrachloride (CCl 4 ) in mice, BMP7 protein expression first increased, followed by a decrease; there was a similar trend in the human body. This process was accompanied by a sustained increase in TGF-β1 protein expression. In vitro experiment results showed that TGF-β1 inhibited BMP7 expression in a time- and dose-dependent manner. In contrast, high doses of exogenous BMP7 inhibited TGF-β1-induced activation, migration, and proliferation of HSCs; this inhibitory effect was associated with upregulation of pSmad1/5/8 and downregulation of phosphorylation of Smad3 and p38 by BMP7. In vivo experiment results showed that exogenous BMP7 improved liver fibrosis in mice. CONCLUSION During liver fibrosis, BMP7 protein expression first increases and then decreases. This changing trend is associated with inhibition of BMP7 expression by sustained upregulation of TGF-β1 in a time- and dose-dependent manner. Exogenous BMP7 could selectively regulate TGF-β/Smad pathway-associated factors to inhibit activation, migration, and proliferation of HSCs and exert anti-liver fibrosis functions. Exogenous BMP7 has the potential to be used as an anti-liver fibrosis drug.

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BMP-7 suppresses excessive scar formation by activating the BMP-7/Smad1/5/8 signaling pathway

Cited by 29 publications

References 28 publications

Fractional CO2 laser combined with 595-nm PDL inhibiting hypertrophic scars via measuring BMP-7 and Fas expression in rabbit models

Fractional CO2 laser combined with 595-nm PDL inhibiting hypertrophic scars via measuring BMP-7 and Fas expression in rabbit models

Correlation between serum transforming growth factor β1, interleukin‑6 and neonatal respiratory distress syndrome

Bone morphogenetic protein-7 represses hepatic stellate cell activation and liver fibrosis via regulation of TGF-β/Smad signaling pathway

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