Negative Effect of Transforming Growth Factor-Beta-1 on Intestinal Anastomotic Tissue Regeneration

Abstract

To examine the involvement of transforming growth factor-β₁(TGF-β₁) in intestinal anastomotic repair, we administered a TGF-β₁-neutralizing antibody to rats after operation, and then examined its influence on the healing process and interaction with other peptide growth factors. Thirty male Sprague-Dawley rats were subjected to primary anastomosis after transection of the small intestine (n = 30) and treated by intraperitoneal administration of IgG (n = 15) or the TGF-β₁ neutralizing antibody (n = 15). Treatment with the antibody against TGF-β₁ resulted in more definite mucosal growth and increased vascularity on day 5 after surgery. Augmented mRNA expression of epidermal growth factor and vascular endothelial growth factor, and an increased number of cells that expressed these peptides in granulation tissue were demonstrated by RT-PCR and immunohistochemical staining. Taken together it was indicated that TGF-β₁ has negative effects on regeneration of the bowel wall mucosa and angiogenesis in the course of intestinal anastomotic wound healing.

Early Growth Response Gene 1–mediated Apoptosis Is Essential for Transforming Growth Factor β1–induced Pulmonary Fibrosis

“…Surprisingly, the degree to which TGF-␤ 1 can account for the varied pathologies in these disorders and the mechanism and reversibility of TGF-␤ 1 -induced fibrosis are poorly understood. In addition, our knowledge of TGF-␤ effector pathways is limited and does not explain how TGF-␤ 1 stimulates fibrosis while simultaneously inducing structural cell apoptosis and tissue injury, and inhibiting epithelialization and wound healing (23)(24)(25)(26)(27). Lastly, because TGF-␤ 1 -induced fibrosis and apoptosis are considered distinct tissue responses, the role of apoptosis in TGF-␤ 1 -induced fibrosis has not been defined.…”

P21 Regulates TGF-β1–Induced Pulmonary Responses via a TNF-α–Signaling Pathway

“…A number of studies demonstrate that, in the proper setting, TGF-b 1 is essential for wound healing, stimulates matrix molecule deposition and angiogenesis, and is an essential mediator of the pathologic scarring in fibrotic disorders (2)(3)(4)(5)(6). On the other hand, TGF-b 1 can also induce tissue injury and cellular apoptosis, decrease epithelialization, and inhibit wound healing (7)(8)(9)(10)(11)(12). The ''contradictory'' and complex nature of these responses reflects an inadequate understanding of the mechanisms that TGF-b 1 uses to induce tissue responses.…”

Cytokines and Growth Factors Promote Airway Smooth Muscle Cell Proliferation

“…Specifically, TGF stimulates proliferation of confluent vascular smooth muscle cells and ASMCs, but inhibits the proliferation of the same cells when they are subconfluent [40–43]. Also in a low dose TGF- β 1 stimulates proliferation of fibroblasts, chondrocytes, and arterial smooth muscle cells, but a high dose of TGF- β 1 inhibits the proliferation of the same cells [39–44]. The induction of proliferation of bovine tracheal ASMCs in the presence of TGF is accompanied by activation of the MAPK pathway [37, 45].…”