Anti-TGFβ1 antibody for modulation of expression of endogenous transforming growth factor beta 1 to prevent fibrosis after plastic surgery in rats

Schultze‐Mosgau, Stefan; Wehrhan, Falk; Rödel, Franz; Amann, Kerstin; Radespiel‐Tröger, Martin; Kopp, Juergen; Grabenbauer, Gerhard G.

doi:10.1016/s0266-4356(03)00257-2

Cited by 19 publications

(9 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In mammals, wound healing often results in scar formation which is regulated by TGF-β signaling [27], [69], [84]. Many studies have reported reduction of scarring in mammals when wounds are treated with chemical inhibitors or specific antibodies aimed at TGF-β isoforms (particularly TGF-β1) during the healing process [66]–[68], [85]–[89]. The situation seems to be very different in the axolotl as blocking of TGF-β signaling prevented limb regeneration.…”

Section: Discussionmentioning

confidence: 99%

Transforming Growth Factor: β Signaling Is Essential for Limb Regeneration in Axolotls

et al. 2007

View full text Add to dashboard Cite

Axolotls (urodele amphibians) have the unique ability, among vertebrates, to perfectly regenerate many parts of their body including limbs, tail, jaw and spinal cord following injury or amputation. The axolotl limb is the most widely used structure as an experimental model to study tissue regeneration. The process is well characterized, requiring multiple cellular and molecular mechanisms. The preparation phase represents the first part of the regeneration process which includes wound healing, cellular migration, dedifferentiation and proliferation. The redevelopment phase represents the second part when dedifferentiated cells stop proliferating and redifferentiate to give rise to all missing structures. In the axolotl, when a limb is amputated, the missing or wounded part is regenerated perfectly without scar formation between the stump and the regenerated structure. Multiple authors have recently highlighted the similarities between the early phases of mammalian wound healing and urodele limb regeneration. In mammals, one very important family of growth factors implicated in the control of almost all aspects of wound healing is the transforming growth factor-beta family (TGF-β). In the present study, the full length sequence of the axolotl TGF-β1 cDNA was isolated. The spatio-temporal expression pattern of TGF-β1 in regenerating limbs shows that this gene is up-regulated during the preparation phase of regeneration. Our results also demonstrate the presence of multiple components of the TGF-β signaling machinery in axolotl cells. By using a specific pharmacological inhibitor of TGF-β type I receptor, SB-431542, we show that TGF-β signaling is required for axolotl limb regeneration. Treatment of regenerating limbs with SB-431542 reveals that cellular proliferation during limb regeneration as well as the expression of genes directly dependent on TGF-β signaling are down-regulated. These data directly implicate TGF-β signaling in the initiation and control of the regeneration process in axolotls.

show abstract

Section: Discussionmentioning

confidence: 99%

Transforming Growth Factor: β Signaling Is Essential for Limb Regeneration in Axolotls

et al. 2007

View full text Add to dashboard Cite

show abstract

“…In a number of fibrotic diseases, TGF-β1 expression is upregulated, and it can induce transdifferentiation of parenchymal cells towards matrix-producing cells [13,14] . Furthermore, TGF-β1 is reported to be involved in promoting cells to synthesize and secret extracellular matrix protein and inhibit its degradation [15][16][17][18][19] . At present research, it was found that specifically blocking TGF-β1 and its receptors, or molecules channels, can effectively delay/reduce fibrosis of denervated skeletal muscle.…”

Section: Disscussionmentioning

confidence: 99%

“…Both RT-PCR and Western blot demonstrated that after nerve injury, the expression of TGF-β1 in the gastrocnemius muscle was increased significantly, accompanied with the increased expression of COL Ⅰ. Local injection of specific antibody was used to block the function TGF-β1 [17,21] . In group C, muscle fibrosis was reduced significantly.…”

Section: Disscussionmentioning

confidence: 99%

Role of transforming growth factor-β1 in the process of fibrosis of denervated skeletal muscle

Fanbin

Chen

Liu

et al. 2011

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

View full text Add to dashboard Cite

In order to investigate the biological function of transforming growth factor-β1 (TGF-β1) during fibrosis in denervated skeletal muscle, we recruited sciatic nerve injury model of SD rats in which denervated gastrocnemius was isolated for analysis. At different time points after operation, denervated muscle was examined by several methods. Masson trichrome staining showed morphological changes of denervated skeletal muscle. Quantitative RT-PCR detected the rapid increase of TGF-β1 expression at mRNA level after nerve injury. It was found that a peak of TGF-β1 mRNA expression appeared one week post-operation. The expression of collagen I (COL I) mRNA was up-regulated in the nerve injury model as well, and reached highest level two weeks post-injury. Immunoblot revealed similar expression pattern of TGF-β1 and COL I in denervated muscles at protein level. In addition, we found that the area of the gastrocnemius muscle fiber was decreased gradually along with increased interstitital fibrosis. Interestingly, this pathological change could be prevented, at least partly, by local injection of TGF-β1 antibodies, which could be contributed to the reduced production of COL I by inhibiting function of TGF-β1. Taken together, in this study, we demonstrated that the expression of TGF-β1 was increased significantly in denervated skeletal muscle, which might play a crucial role during muscle fibrosis after nerve transection.

show abstract

“…For safety purposes, long-term studies on larger animals are necessary in order to predict whether or not a given therapeutic approach will be efficient and without side effects in humans. [16,[20][21][22] Express BMP-7 and HGF [23,73] Immunogenicity Downregulation of MHC class I and co-receptor molecules siRNA, anti-sense RNA, express CTLA-4 Ig [34,110] Autoimmune disease TNF, pro-inflammatory cytokines Express soluble proinflammatory cytokine receptors [110] Express anti-inflammatory cytokines [110] Control unwanted growth Pro-drug activating enzymes Expressing HSV-tk [5] Direct differentiation to a particular pathway Transcription factors Such as Brachyury, Myo-D, Nurr-1, RunX1/Cbfa-1, Pax-6, Neuro-D and β-cellulin [77][78][79][80][81][82][83][84][85][86] Growth/differentiation factors Such as BMP-2,-4, TGF-β, IGF-1 and GDNF [87][88][89][90][91] BMP: Bone morphogenetic protein; IGF: Insulin growth factor; siRNA: Small interfering RNA; TGF:Transforming growth factor.…”

Section: Future Perspectivementioning

confidence: 99%

Engineering Stem Cells for Therapy

et al. 2006

View full text Add to dashboard Cite

The differentiation of a stem cell is dependent on the environmental cues that it receives and can be modulated by the expression of different master regulators or by secreted factors or inducers. The use of genetically modified stem cells to express the required factors can direct differentiation along the requisite pathway. This approach to the engineering of stem cells is important, as control of the pluripotentiality of stem cells is necessary in order to avoid unwanted growth, migration or differentiation to nontarget tissues. The authors provide an overview of the stem cell engineering field, highlighting challenges and solutions, and focusing on recent developments in therapeutic applications in areas such as autoimmunity, CNS lesions, bone and joint diseases, cancer and myocardial infarction.

show abstract

Anti-TGFβ1 antibody for modulation of expression of endogenous transforming growth factor beta 1 to prevent fibrosis after plastic surgery in rats

Cited by 19 publications

References 20 publications

Transforming Growth Factor: β Signaling Is Essential for Limb Regeneration in Axolotls

Transforming Growth Factor: β Signaling Is Essential for Limb Regeneration in Axolotls

Role of transforming growth factor-β1 in the process of fibrosis of denervated skeletal muscle

Engineering Stem Cells for Therapy

Contact Info

Product

Resources

About