Up-regulation of CREB-1 regulates tendon adhesion in the injury tendon healing through the CREB-1/TGF-β3 signaling pathway.

Publisher: BioMed Central Country of Publication: England NLM ID: 100968565 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2474 (Electronic) Linking ISSN: 14712474 NLM ISO Abbreviation: BMC Musculoskelet Disord Subsets: MEDLINE

Original Publication: London : BioMed Central, [2000-

Tendon Injuries*/metabolism ; Cyclic AMP Response Element-Binding Protein*/metabolism ; Wound Healing* ; Transforming Growth Factor beta3*/metabolism; Animals ; Mice ; Tendons ; Signal Transduction ; Mice, Inbred C57BL ; Male ; Stem Cells ; Gait Analysis ; Tissue Adhesions/prevention & control

Aim: To explore the mechanism of the healing of tendon tissue and anti-adhesion, and to discuss the role of the transforming growth factor-β3 (TGF-β3)/cAMP response element binding protein-1 (CREB-1) signaling pathway in the healing process of tendons.
Method: All mice were divided into four groups of 1, 2, 4, and 8 weeks respectively. Each time group was divided into four treatment groups: the amplification group, the inhibition group, the negative group, and the control group. When the tendon injury model was established, the CREB-1 virus was injected into the tendon injury parts. A series of methods such as gait behaviourism, anatomy, histological examination, immunohistochemical examination and collagen staining were employed to assess the tendon healing and the protein expression of TGF-β3, CREB-1, Smad3/7 and type I/III collagen (COL-I/III). CREB-1 virus was sent to tendon stem cells to assess the protein expression of TGF-β1, TGF-β3, CREB-1, COL-I/III by methods such as immunohistochemistry and Western blot.
Results: The amplification group showed better gait behaviourism than the inhibition group in the healing process. The amplification group also had less adhesion than the negative group. Hematoxylin-eosin (HE) staining of tendon tissue sections showed that the number of fibroblasts in the amplification group was less than the inhibition group, and the immunohistochemical results indicated that the expression of TGF-β3, CREB-1, and Smad7 at each time point was higher than the inhibition group. The expression of COL-I/III and Smad3 in the amplification group was lower than the inhibition group at all time points. The collagen staining indicated that the ratio of type I/III collagen in the amplification group was higher than the negative group at 2,4,8 week. The CREB-1 amplification virus could promote the protein expression of TGF-β3, CREB-1 and inhibit the protein expression of TGF-β1 and COL-I/III in the tendon stem cells.
Conclusion: In the process of tendon injury healing, CREB-1 could promote the secretion of TGF-β3, so as to promote the tendon healing and have the effect of anti-adhesion in tendons. It might provide new intervention targets for anti-adhesion treatment of tendon injuries.
(© 2023. The Author(s).)

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Keywords: Adhesion2; CREB-15; Healing3; TGF-β34; Tendon1

0 (Creb1 protein, mouse)
0 (Cyclic AMP Response Element-Binding Protein)
0 (Tgfb3 protein, mouse)
0 (Transforming Growth Factor beta3)

Date Created: 20230425 Date Completed: 20230718 Latest Revision: 20230718

20250114

PMC10127358

10.1186/s12891-023-06425-7

37098516