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1.
J Cell Sci ; 136(18)2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37667902

RESUMO

Liver injury leads to fibrosis and cirrhosis. The primary mechanism underlying the fibrogenic response is the activation of hepatic stellate cells (HSCs), which are 'quiescent' in normal liver but become 'activated' after injury by transdifferentiating into extracellular matrix (ECM)-secreting myofibroblasts. Given that integrins are important in HSC activation and fibrogenesis, we hypothesized that paxillin, a key downstream effector in integrin signaling, might be critical in the fibrosis pathway. Using a cell-culture-based model of HSC activation and in vivo models of liver injury, we found that paxillin is upregulated in activated HSCs and fibrotic livers. Overexpression of paxillin (both in vitro and in vivo) led to increased ECM protein expression, and depletion of paxillin in a novel conditional mouse injury model reduced fibrosis. The mechanism by which paxillin mediated this effect appeared to be through the actin cytoskeleton, which signals to the ERK pathway and induces ECM protein production. These data highlight a novel role for paxillin in HSC biology and fibrosis.


Assuntos
Actinas , Células Estreladas do Fígado , Camundongos , Animais , Paxilina/genética , Paxilina/metabolismo , Actinas/metabolismo , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Polimerização , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Fígado/metabolismo , Fibrose , Modelos Animais de Doenças
2.
Surg Technol Int ; 44: 71-86, 2024 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-39083445

RESUMO

Cellular and matrix-like products come in many forms. Among them, powdered and micronized formulations have become increasingly available and popular owing to their unique properties and advantages. Powders have increased tissue contact which many believe can enhance granulation tissue formation, they fill irregular and deep cavities, and they can be used in concert with sheet-like products and skin grafts for improved healing. Despite their advantages, powdered products do have certain limitations that hinder their use, including poor insurance coverage and a lack of CPT coding for adequate reimbursement in an outpatient setting, making their use primarily limited to the operating room. Also, most published data on powdered products consists of smaller case studies and case series, with few reports evaluating the efficacy and utility of powdered formulations compared to their sheet-like progenitors. In this manuscript, we organize available powdered matrix products by type of substrate: xenograft, allograft, placental-based, and synthetic, and review the data in support of various products in specific wound types. This review of the supporting literature provides the current body of evidence on the utility of powdered matrices in wounds.


Assuntos
Pós , Cicatrização , Humanos , Cicatrização/fisiologia , Transplante de Pele/métodos , Animais , Regeneração/fisiologia
3.
Histochem Cell Biol ; 158(4): 325-334, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35960334

RESUMO

Ongoing liver injury leads to fibrosis and ultimately cirrhosis, a leading cause of death worldwide. The primary mechanism underlying the fibrogenic response is the activation of cells known as hepatic stellate cells (HSCs) which are "quiescent" in the normal liver but become "activated" after injury by transdifferentiating into extracellular matrix-secreting myofibroblasts. Since integrins (extracellular matrix binding receptors) are important mediators of HSC activation and fibrogenesis, we hypothesized that focal adhesion (FA) proteins, which link integrins to the intracellular protein machinery, may be important in the activation process. Therefore, using both an in vitro model of activation in primary rat HSCs and an in vivo model of liver injury, we examined three FA proteins: vinculin, FAK, and talin. All three proteins were significantly upregulated during HSC activation at both the messenger RNA (mRNA) and protein levels. Confocal microscopy demonstrated that the proteins had a widespread expression throughout HSCs with prominent localization at the end of actin filaments. Finally, we stimulated HSCs with the profibrotic ligands endothelin-1 (ET-1) and transforming growth factor beta (TGF-ß) and observed an increase in the size of vinculin-containing FAs and the cell area occupied by them. The data indicate that HSCs possess a broad array of FA proteins, and given their upregulation during activation, this raises the possibility that they play a role in the fibrogenic response to injury.


Assuntos
Adesões Focais , Células Estreladas do Fígado , Animais , Células Cultivadas , Endotelina-1/metabolismo , Adesões Focais/metabolismo , Células Estreladas do Fígado/metabolismo , Integrinas/metabolismo , Ligantes , Fígado/metabolismo , RNA Mensageiro/metabolismo , Ratos , Roedores/metabolismo , Talina/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Vinculina/metabolismo
4.
Biocell ; 46(9): 2003-2007, 2022 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-35734751

RESUMO

Hepatic stellate cells (HSCs) are the primary effector cells in liver fibrosis. In the normal liver, HSCs serve as the primary vitamin A storage cells in the body and retain a "quiescent" phenotype. However, after liver injury, they transdifferentiate to an "activated" myofibroblast-like phenotype, which is associated with dramatic upregulation of smooth muscle specific actin and extracellular matrix proteins. The result is a fibrotic, stiff, and dysfunctional liver. Therefore, understanding the molecular mechanisms that govern HSC function is essential for the development of anti-fibrotic medications. The actin cytoskeleton has emerged as a key component of the fibrogenic response in wound healing. Recent data indicate that the cytoskeleton receives signals from the cellular microenvironment and translates them to cellular function-in particular, increased type I collagen expression. Dynamic in nature, the actin cytoskeleton continuously polymerizes and depolymerizes in response to changes in the cellular microenvironment. In this viewpoint, we discuss the recent developments underlying cytoskeletal actin dynamics in liver fibrosis, including how the cellular microenvironment affects HSC function and the molecular mechanisms that regulate the actin-induced increase in collagen expression typical of activated HSCs.

5.
Heliyon ; 10(11): e31854, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38867978

RESUMO

In this study, TiO2 supported over embryonic Beta zeolite (BEA) was prepared for the photocatalytic degradation of Tetracycline (TC) antibiotic under visible light. The immobilization of sol-gel TiO2 over the zeolite increased its surface area from 33 (m2/g) to 226 (m2/g) and enhanced its adsorption efficiency from 8 % to 18 %. In order to expand the photocatalytic activity of TiO2 towards the visible light region (i.e. λ > 380 nm), two different metal sensitization techniques with Iron ions from aqueous solution of FeCl3 were explored. In the ion-exchange method, the substitutional cations within the TiO2/BEA structure were exchanged with Fe3+. Whereas, in the doping technique, solgel TiO2 was doped with Fe3+ during its synthesis and before its immobilization over Zeolite. Four different samples with 20, 40, 60, and 100 % w/w of TiO2/BEA ratio were prepared. After testing the various ion-exchanged photocatalysts under blue and white lights, only Fe-60%TiO2/BEA showed better activity compared to pure TiO2 under white light at TC initial concentration, C o = 20 ppm. For the doped immobilized Titania with 60 wt% TiO2/BEA, three different doped photocatalysts were prepared with 3 %, 7 %, and 10 % per mole Fe/TiO2. All the Fe-doped TiO2/BEA photocatalysts showed better activity compared to pure TiO2 under white light. Under solar irradiations, the 3 % Fe-doped TiO2/BEA was able to degrade all TC within 120 min, while Fe-60%TiO2/BEA needed 200 min, and TiO2 needed more than 300 min. This enhanced performance was a result of both increased surface area due to immobilization over BEA as well as iron doping by Fe3+ that simultaneously increased the visible light absorption of TiO2 and minimized the charge carrier recombination effect.

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