Inhibition of Smad3 Expression in Radiation-Induced Fibrosis Using a Novel Method for Topical Transcutaneous Gene Therapy

Lee, Judy W.; Tutela, John Paul; Zoumalan, Richard A.; Thanik, Vishal; Nguyen, Phuong D.; Varjabedian, L; Warren, Stephen M.; Saadeh, Pierre B.

doi:10.1001/archoto.2010.107

Cited by 38 publications

(41 citation statements)

References 22 publications

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“…Accordingly, transcutaneous delivery of Smad3 siRNA decreases radiation-induced skin fibrosis as compared with control siRNA. 171 Future studies targeting other components of the TGF-b signaling pathway to modulate wound healing and scarring outcome are eagerly awaited. Figure 8 depicts strategies for targeting the TGF-b pathway to improve wound healing outcome as described earlier.…”

Section: Strategies Used For Targeting the Tgf-b Signaling Pathway Tomentioning

confidence: 99%

Dynamics of Transforming Growth Factor Beta Signaling in Wound Healing and Scarring

Finnson

McLean

Guglielmo

et al. 2013

Advances in Wound Care

247

222

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Section: Strategies Used For Targeting the Tgf-b Signaling Pathway Tomentioning

confidence: 99%

Dynamics of Transforming Growth Factor Beta Signaling in Wound Healing and Scarring

Finnson

McLean

Guglielmo

et al. 2013

Advances in Wound Care

247

222

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“…Therefore, other effective targets for inhibiting the downstream activity of TGF-b/Smad signaling could be Smad3 or TGF-b receptors, including TGFBRI, TGFBRII, and TGFBRIII. In fact, wound scarring has been shown to be reduced by downregulating expression of Smad3 (Sekiguchi et al, 2007;Wang et al, 2007;Lee et al, 2010) or TGFBRII protein expression (Nakamura et al, 2004;Chu et al, 2008). In addition, overexpression of dominant negative mutant TGFBRII has been used to inhibit TGF-b binding to normal TGF-b receptors (Reid et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

siRNA-Targeting Transforming Growth Factor-β Type I Receptor Reduces Wound Scarring and Extracellular Matrix Deposition of Scar Tissue

Wang

Liou

Cherng

et al. 2014

Journal of Investigative Dermatology

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Hypertrophic scarring is related to persistent activation of transforming growth factor-β (TGF-β)/Smad signaling. In the TGF-β/Smad signaling cascade, the TGF-β type I receptor (TGFBRI) phosphorylates Smad proteins to induce fibroblast proliferation and extracellular matrix deposition. In this study, we inhibited TGFBRI gene expression via TGFBRI small interfering RNA (siRNA) to reduce fibroblast proliferation and extracellular matrix deposition. Our results demonstrate that downregulating TGFBRI expression in cultured human hypertrophic scar fibroblasts significantly suppressed cell proliferation and reduced type I collagen, type III collagen, fibronectin, and connective tissue growth factor (CTGF) mRNA, and type I collagen and fibronectin protein expression. In addition, we applied TGFBRI siRNA to wound granulation tissue in a rabbit model of hypertrophic scarring. Downregulating TGFBRI expression reduced wound scarring, the extracellular matrix deposition of scar tissue, and decreased CTGF and α-smooth muscle actin mRNA expression in vivo. These results suggest that TGFBRI siRNA could be applied clinically to prevent hypertrophic scarring.

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“…Lee et al first delivered Smad3 siRNA to inhibit skin fibrosis induced by radiation. 143 Similarly, Wang et al inhibited TGF-b/Smad signaling by applying TGF-b1 receptor siRNA and reported reduced hypertrophic scarring. 144 To sustain the release of these TGF-b/Smad targeting siRNAs, delivery matrices, including trimethyl chitosan 145 and pressure-sensitive hydrogels, 146 were developed.…”

Section: 81mentioning

confidence: 99%

Biochemical and Biophysical Cues in Matrix Design for Chronic and Diabetic Wound Treatment

Xiao

Ahadian

Radišić

2017

Tissue Engineering Part B: Reviews

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Progress in biomaterial science and engineering and increasing knowledge in cell biology have enabled us to develop functional biomaterials providing appropriate biochemical and biophysical cues for tissue regeneration applications. Tissue regeneration is particularly important to treat chronic wounds of people with diabetes. Understanding and controlling the cellular microenvironment of the wound tissue are important to improve the wound healing process. In this study, we review different biochemical (e.g., growth factors, peptides, DNA, and RNA) and biophysical (e.g., topographical guidance, pressure, electrical stimulation, and pulsed electromagnetic field) cues providing a functional and instructive acellular matrix to heal diabetic chronic wounds. The biochemical and biophysical signals generally regulate cell-matrix interactions and cell behavior and function inducing the tissue regeneration for chronic wounds. Some technologies and devices have already been developed and used in the clinic employing biochemical and biophysical cues for wound healing applications. These technologies can be integrated with smart biomaterials to deliver therapeutic agents to the wound tissue in a precise and controllable manner. This review provides useful guidance in understanding molecular mechanisms and signals in the healing of diabetic chronic wounds and in designing instructive biomaterials to treat them.

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Inhibition of Smad3 Expression in Radiation-Induced Fibrosis Using a Novel Method for Topical Transcutaneous Gene Therapy

Abstract: Smad3 expression can be effectively silenced in vivo using a novel topical delivery system. Moreover, cutaneous Smad3 inhibition mitigates radiation-induced changes in tissue elasticity, restoring a near-normal phenotype.

Cited by 38 publications

References 22 publications

Dynamics of Transforming Growth Factor Beta Signaling in Wound Healing and Scarring

Dynamics of Transforming Growth Factor Beta Signaling in Wound Healing and Scarring

siRNA-Targeting Transforming Growth Factor-β Type I Receptor Reduces Wound Scarring and Extracellular Matrix Deposition of Scar Tissue

Biochemical and Biophysical Cues in Matrix Design for Chronic and Diabetic Wound Treatment

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