TGF-β3 Stimulates and Regulates Collagen Synthesis Through TGF-β1-Dependent and Independent Mechanisms

Abstract

In contrast to the TGF-beta1 and beta2 isoforms, TGF-beta3 has shown the ability to downregulate scarring and fibrosis in vivo under certain experimental conditions. In this study, we determined the direct effects of TGF-beta3 on cultures of human dermal fibroblasts. TGF-beta3 (0.1 to 100 pg per ml) increased DNA synthesis up to 50% (p < 0.01, r = 0.970), collagen protein synthesis up to 200% (dose range of 0.1 to 5 ng per ml, p < 0.001, r = 0.990), and increased alpha1(I) procollagen mRNA levels (r = 0.999), with maximal effects (200% of control) observed by 24 h. Collagen lattice contraction was increased by more than 50% in response to TGF-beta3 (p < 0.001), and to a similar extent as the TGF-beta1 isoform. Stimulation of collagen synthesis and of alpha1(I) procollagen mRNA levels in response to TGF-beta3 was partially blocked by a TGF-beta1-specific anti-sense oligonucleotide but was still detectable (35% greater than baseline) when TGF-beta3 was added to dermal fibroblasts from TGF-beta1 knock-out mice. In contrast with these stimulatory effects, however, downregulation of alpha1(I) procollagen, alpha1(III) procollagen, and TGF-beta1 mRNA levels toward baseline occurred when TGF-beta3 (0.1 to 5 ng per ml) was added simultaneously and in combination with TGF-beta1. We conclude that stimulation of collagen synthesis by TGF-beta3 occurs through TGF-beta1-dependent and independent pathways. By downregulating the response to TGF-beta1 and by shifting from one pathway to the other, TGF-beta3 can dampen and provide fine-tuning to the overall TGF-beta's induced program of collagen deposition.

Reversible remodeling of lung tissue during hibernation in the Syrian hamster

“…Although the mechanism is not clear, the substantial increase in collagen content in early torpor may be related to changes occurring in some of the remodeling-associated proteins, as it coincides with upregulation of TGF- and ACE and the downregulation of caveolin-1. TGF- has been implicated in collagen deposition in the lung (Murata et al, 1997). Moreover, a decreased expression of caveolin-1 has been associated with enhanced TGF- signaling and increased collagen deposition (Le Lay and Kurzchalia, 2005).…”

Fibrin Gels Exhibit Improved Biological, Structural, and Mechanical Properties Compared with Collagen Gels in Cell-Based Tendon Tissue-Engineered Constructs

“…Fibrin gels were created as previously described 28 at a final concentration of 3.4 mg/mL bovine fibrinogen (SigmaAldrich; St. Louis, MO) and 4 U/mL bovine thrombin (Sigma). TECs were fed every 2 days with culture medium (MEM a, 10% FBS, and 1% antibiotic/antimycotic) supplemented with 200 mM l-ascorbic acid 2-phosphate (Sigma) and 20 ng/mL TGFb-3 (Peprotech; Rocky Hill, NJ) to stimulate collagen synthesis [41][42][43] and incubated at 37°C, 5% CO 2 , and 95% relative humidity.…”

“…(3) We stimulated TECs with TGFb-3 supplemented medium, because fibrin TECs failed to form and collagen TECs failed to contract without this growth factor. Since TGFb-3 regulates collagen synthesis and other tendon markers, 42,69,70 its presence may have affected interactions among material and time or masked the effects of mechanical stimulation. Future research will focus on how TGFb-3 and other growth factors influence expression of such tenogenic markers in progenitor cells.…”

Selective Expression of TGF-β2 and TGF-β3 Isoforms in Early Mesangioproliferative Glomerulonephritis

“…In fact, TGF-β3 counteracted the effects of TGF-β1 on collagen production, an integral component of extracellular matrix [27]. Taken together, these and other studies suggest that different TGF-β isoforms have distinct and separable roles in experimental models of disease and that the study of a particular isoform in isolation may not adequately represent the in vivo situation.…”