Mechanism of the transforming growth factor-β induction of fibronectin expression in hepatic stem-like cells

Cui, Wei; Jin, Hongwei; Li, Z.W.

doi:10.1590/s0100-879x2009007500017

Cited by 13 publications

(10 citation statements)

References 29 publications

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“…Nuclear Smad oligomers bind to DNA and associate with transcription factors to regulate expression of target genes [21], [22]. In the process of tissue fibrosis, TGF-β1 is likely to facilitate the expression of the extracellular matrix gene to increase the synthesis and deposition of collagen, fibronectin, and proteoglycan [23], [24]. While, simultaneously, decreasing the yield of cathepsin and enhancing the synthesis of cathepsin inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Effects of TRAP-1-Like Protein (TLP) Gene on Collagen Synthesis Induced by TGF-β/Smad Signaling in Human Dermal Fibroblasts

et al. 2013

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BackgroundHypertrophic scars are pathologic proliferations of the dermal skin layer resulting from excessive collagen deposition during the healing process of cutaneous wounds. Current research suggests that the TGF-β/Smad signaling pathway is closely associated with normal scar and hypertrophic scar formation. TRAP-1-like protein (TLP), a cytoplasmic protein, has been reported to efficiently regulate Smad2- and Smad3-dependent signal expression in the TGF-β pathway. The relationship between TLP and Type I/III collagen (Col I/III) synthesis explored in the present study provides an effective target for wound healing and gene therapy of hypertrophic scarring.ObjectiveTo investigate the effects of TLP on collagen synthesis in human dermal fibroblasts. MethodsLentiviral vectors encoding TLP was constructed to transfect fibroblasts derived from normal human skin. The expression of Col I/III and phosphorylation of Smad2 and Smad3 in fibroblasts were examined after TLP treatment. In addition, the comparison of TLP expression in normal skin tissues and in hypertrophic scar tissues was performed, and the effect of TLP on cell viability was analyzed by MTT assay.ResultsTLP expression in hypertrophic scar tissue was markedly higher than in normal skin tissue. The Real Time PCR and Western blot test results both revealed that the synthesis of Col I/III was positively correlated with the expression of TLP. TLP also facilitate Smad2 phosphorylation while, conversely, inhibiting Smad3 phosphorylation. TLP may play a cooperative role, along with the cytokine TGF-β1, in improving the overall cell viability of skin fibroblasts.ConclusionsTLP likely acts as a molecular modulator capable of altering the balance of Smad3- and Smad2-dependent signaling through regulation of phosphorylation, thus facilitating collagen synthesis in fibroblasts. Based on genetic variation in TLP levels in different tissues, these results suggest that TLP plays a key role in the process of TGF-β1/Smad3 signaling that contributes to wound healing and genesis of pathologic scars.

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Section: Discussionmentioning

confidence: 99%

Effects of TRAP-1-Like Protein (TLP) Gene on Collagen Synthesis Induced by TGF-β/Smad Signaling in Human Dermal Fibroblasts

et al. 2013

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“…Nuclear Smad oligomers bind to DNA and associate with transcription factors to regulate expression of target genes [38, 39]. In the process of tissue fibrosis, TGF-β1 is likely to facilitate the expression of the ECM genes for an increase in the synthesis and deposition of collagen, fibronectin, and proteoglycan [40]. …”

Section: Discussionmentioning

confidence: 99%

Regeneration of full-thickness skin defects by differentiated adipose-derived stem cells into fibroblast-like cells by fibroblast-conditioned medium

et al. 2017

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BackgroundFibroblasts are ubiquitous cells in the human body and are absolutely necessary for wound healing such as for injured skin. This role of fibroblasts was the reason why we aimed to differentiate human adipose-derived stem cells (hADSCs) into fibroblasts and to test their wound healing potency. Recent reports on hADSC-derived conditioned medium have indicated stimulation of collagen synthesis as well as migration of dermal fibroblasts in wound sites with these cells. Similarly, human fibroblast-derived conditioned medium (F-CM) was reported to contain a variety of factors known to be important for growth of skin. However, it remains unknown whether and how F-CM can stimulate hADSCs to secrete type I collagen.MethodsIn this study, we obtained F-CM from the culture of human skin fibroblast HS27 cells in DMEM media. For an in-vivo wound healing assay using cell transplantation, balb/c nude mice with full-thickness skin wound were used.ResultsOur data showed that levels of type I pro-collagen secreted by hADSCs cultured in F-CM increased significantly compared with hADSCs kept in normal medium for 72 h. In addition, from a Sircol collagen assay, the amount of collagen in F-CM-treated hADSC conditioned media (72 h) was markedly higher than both the normal medium-treated hADSC conditioned media (72 h) and the F-CM (24 h). We aimed to confirm that hADSCs in F-CM would differentiate into fibroblast cells in order to stimulate wound healing in a skin defect model. To investigate whether F-CM induced hADSCs into fibroblast-like cells, we performed FACS analysis and verified that both F-CM-treated hADSCs and HS27 cells contained similar expression patterns for CD13, CD54, and CD105, whereas normal medium-treated hADSCs were significantly different. mRNA level analysis for Nanog, Oct4A, and Sox2 as undifferentiation markers and vimentin, HSP47, and desmin as matured fibroblast markers supported the characterization that hADSCs in F-CM were highly differentiated into fibroblast-like cells. To discover the mechanism of type I pro-collagen expression in hADSCs in F-CM, we observed that phospho-smad 2/3 levels were increased in the TGF-β/Smad signaling pathway. For in-vivo analysis, we injected various cell types into balb/c nude mouse skin carrying a 10-mm punch wound, and observed a significantly positive wound healing effect in this full-thickness excision model with F-CM-treated hADSCs rather than with untreated hADSCs or the PBS injected group.ConclusionsWe differentiated F-CM-treated hADSCs into fibroblast-like cells and demonstrated their efficiency in wound healing in a skin wound model.

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“…Такі молекули називають цитокінами. Сьогодні під цитокінами розуміють велику кількість різноманітних біологічно активних молекул білкової природи, що секретуються клітинами імунної системи при запаленні, імунній відповіді, гемопоезі тощо [14][15][16].…”

Section: вступunclassified

“…Цитокіни є найбільш універсальною системою регуляції, що здатна проявляти біологічну активність як дистанційно, так і при міжклітинному контакті. Цитокіни є системою-організатором організму, яка формує та регулює весь комплекс патоморфологічних зсувів при проникненні патогена [14][15][16][17]. Синтезуючись у вогнищі запалення, вони впливають практично на усі клітини, які беруть участь у вогнищі запалення, а також практично на усі клітини, які беруть участь у розвитку запалення, включаючи гранулоцити, макрофаги, фібробласти, клітини ендотелію, епітелію, Т-та В-лімфоцити [17,18].…”

Section: вступunclassified

Особливості Зміни Показників Прозапальних Цитокінів У Щурів Із Модельованим Галактозаміновим Гепатитом На Тлі Мерказоліліндукованого Гіпотиреозу

Zarichna¹,

Shkliar²,

Кліщ³

2019

BMBR

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Мета роботи. Вивчити зміни показників цитокінового профілю та функціонального стану ендотелію у щурів із мерказоліліндукованим гіпотиреозом і супутнім галактозаміновим гепатитом. Матеріали і методи. Дослідження проводили на білих щурах-самцях масою тіла 180–200 г, яких отримали з віварію Тернопільського національного медичного університету імені І. Я. Горбачевського МОЗ України. Гіпотиреоз моделювали щоденним введенням фармакопейного тиреостатика мерказолілу в дозі 25 мг/кг протягом 21-ї доби per os за допомогою спеціального зонда. Вплив гіпотиреозу на перебіг запального процесу при гепатиті вивчали на моделі галактозамінового гепатиту (ГАГ), який викликали шляхом внутрішньочеревного уведення експериментальним тваринам галактозаміну в дозі 400 мг/кг у вигляді 20 % розчину. Результати й обговорення. Виявлено, що показник TNF-α у тварин із модельованим гіпотиреозом збільшився у 1,05 раза, IL-1α – в 1,41 раза, IL-4 – 1,33 раза, INF-γ – 5,56 раза відносно інтактних тварин. Причому моноцитарний хемоатрактантний протеїн (MCP) зменшився у 0,95 раза. Після модельованого галактозамінового гепатиту виявлено, що показник TNF-α збільшився у 1,13 раза, IL-1α – в 1,49 раза, IL-4 – 1,56 раза, INF-γ – 6,57 раза, MCP – 1,06 раза відносно інтактних тварин. Після модельованого галактозамінового гепатиту на тлі гіпотиреозу відбулись наступні зміни: показник TNF-α збільшився у 1,32 раза, IL-1α – в 1,70 рази, IL-4 – 1,94 раза, INF-γ – 5,89 раза MCP – 1,11 раза відносно інтактних тварин. Висновки. За умов експериментального галактозамінового гепатиту на тлі гіпотиреозу відбувається гіперпродукція інтерлейкіну-1α (IL-1α), інтерлейкіну-4 (IL-4), інтерферону-γ (IFN-γ), фактора некрозу пухлин-α (TNF-α), а також гіпопродукцію моноцитарного хемоатрактантного протеїну, що можуть спричиняти значні зміни в тканинах печінки.

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Mechanism of the transforming growth factor-β induction of fibronectin expression in hepatic stem-like cells

Cited by 13 publications

References 29 publications

Effects of TRAP-1-Like Protein (TLP) Gene on Collagen Synthesis Induced by TGF-β/Smad Signaling in Human Dermal Fibroblasts

Effects of TRAP-1-Like Protein (TLP) Gene on Collagen Synthesis Induced by TGF-β/Smad Signaling in Human Dermal Fibroblasts

Regeneration of full-thickness skin defects by differentiated adipose-derived stem cells into fibroblast-like cells by fibroblast-conditioned medium

Особливості Зміни Показників Прозапальних Цитокінів У Щурів Із Модельованим Галактозаміновим Гепатитом На Тлі Мерказоліліндукованого Гіпотиреозу

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