Synthesis and Formulation of Four-Arm PolyDMAEA-siRNA Polyplex for Transient Downregulation of Collagen Type III Gene Expression in TGF-β1 Stimulated Tenocyte Culture

Abstract Background The injured flexor tendon has poor healing ability, which is easy to cause tendon adhesion. It can affect the recovery of tendon function, which is still a long-term and difficult task for surgeons. Transforming growth factor β (TGF-β) has been widely considered to play an important role in flexor tendon repair in recent years. Aim This work was to investigate the anti-adhesion and anti-inflammatory effects of TGF-β3 on flexor digitorum longus (FDL) tendon repair rats. Method Anastomosis models of tendon laceration in the flexion toes of rats were delivered with no treatment, vehicle, or TGF-β3 -overexpressed adenovirus vector (ad-TGF-β3) locally to the injured tendon area from day 3 to 8. Subsequently, the expression of TGF-β3, TGF-β1/2, Smad3, Smad7, JNK, phosphorylation (p)-JNK, c-Jun, and phosphorylation (p)-c-Jun were detected by western blot, the expression of Mmp9 and Mmp2 by RT-qPCR, the Range of motion (ROM) and gliding resistance by adhesion formation testing, the mechanical strength of tendon healing by biomechanical testing, the pathologic changes of flexor tendon tissues by HE staining, the expression of collagen type III by immunohistochemical staining, and the levels of IL-6, TNF-α, COX2 and IL-1β in serum by ELISA, respectively. Results Rat models treated with no treatment showed a lower elevation of TGF-β3 and Smad7 expression, and a higher elevation of TGF-β1/2 and Smad3 expression, during day 14 to day 28. Besides, under the treatment of ad-TGF-β3, a significantly increase was reflected in the expression of TGF-β3 and Smad7, ROM, as well as mechanical strength of flexor tendon, whereas significantly reduction was shown in gliding resistance, the content of inflammatory cytokines, the ratio of p-JNK/JNK, p-c-Jun/c-Jun, as well as the expression of TGF-β1/2, Smad3, Mmp9, and Mmp2 genes, as compared to those from vehicle treatment. Meanwhile, TGF-β3 demonstrated a better pathologic recovery process with no obvious necrosis or fracture of collagen fibers. Besides, TGF-β3 revealed a significant reduction of collagen type-III expression in the flexor tendon healing tissues. Conclusion These findings suggested that TGF-β3 effectively protected against flexor tendon injury via regulating adhesion formation.

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Right ventricular collagen type III and IV gene expression increases during early phases of endurance training in hypobaric hypoxic condition

Basic Research in Cardiology ◽

10.1007/s003950050039 ◽

1997 ◽

Vol 92 (5) ◽

pp. 299-309

Author(s):

M. Perhonen ◽

W. Wang ◽

X. Han ◽

H. Ruskoaho ◽

T. E. S. Takala

Keyword(s):

Gene Expression ◽

Right Ventricular ◽

Endurance Training ◽

Collagen Type ◽

Hypoxic Condition ◽

Collagen Type Iii ◽

Type Iii ◽

Early Phases

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Right ventricular collagen type III and IV gene expression increases during early phases of endurance training in hypobaric hypoxic condition

Basic Research in Cardiology ◽

10.1007/bf00788942 ◽

1997 ◽

Vol 92 (5) ◽

pp. 299-309 ◽

Cited By ~ 7

Author(s):

M. Perhonen ◽

W. Wang ◽

X. Han ◽

H. Ruskoaho ◽

T. E. S. Takala

Keyword(s):

Gene Expression ◽

Right Ventricular ◽

Endurance Training ◽

Collagen Type ◽

Hypoxic Condition ◽

Collagen Type Iii ◽

Type Iii ◽

Early Phases

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TGF-β3 Regulates Adhesion Formation Through the JNK/c-Jun Pathway During Flexor Tendon Healing

10.21203/rs.3.rs-120031/v1 ◽

2020 ◽

Author(s):

Ke Jiang ◽

Yuling lI ◽

Chao Xiang ◽

Yeshuang Yuan ◽

Jiameng Jia

Keyword(s):

Mechanical Strength ◽

Collagen Type ◽

Flexor Tendon ◽

Adhesion Formation ◽

Tendon Repair ◽

Tendon Healing ◽

Collagen Type Iii ◽

Type Iii ◽

Sliding Resistance ◽

Tgf Β1

Abstract Background: The injured flexor tendon has poor healing ability, 15 which is easy to cause tendon adhesion. It can affect the recovery of tendon function, which is still a long term and difficult task for surgeons. Transforming growth factor β (TGF-β) has been widely considered to play an important role in flexor tendon repair in recent years. Aim: This work was to investigate the anti-adhesion and anti-inflammatory effects of TGF-β3 on flex or digitorum longus (FDL) tendon repair rats. Method: Anastomosis models of tendon laceration in the flexion toes of rats were delivered with no treatment, vehicle or TGF-β3 - overexpressed adenovirus vector (ad-TGF-β3) locally to the injured tendon area from day 3 to 8. Subsequently, the expression of TGF-β3, TGF-β1/2, Smad3, Smad7, JNK, phosphorylation (p)-JNK, c-Jun and phosphorylation (p)-c-Jun were detected by western blot, the expression of Mmp9 and Mmp2 by RT-qPCR, the Range of motion (ROM) and sliding resistance by adhesion formation testing, the mechanical strength of tendon healing by biomechanical testing, the pathologic changes of flexor tendon tissues by HE staining, the expression of collagen type III by immunohistochemical staining, and the levels of IL-6, TNF-α, COX2 and IL-1β in serum by ELISA, respectively. Results: Rat models treated with no treatment showed a lower elevation of TGF-β3 and Smad7 expression, and a higher elevation of TGF-β1/2 and Smad3 expression, during day 14 to day 28. Besides, under the treatment of ad-TGF-β3, significantly increase was reflected in the expression of TGF-β3 and Smad7, ROM, as well as mechanical strength of flexor tendon, whereas significantly reduction was shown in sliding resistance, content of inflammatory cytokines, ratio of p-JNK/JNK, p-c-Jun/c-Jun, as well as the expression of TGF-β1/2, Smad3, Mmp9 and Mmp2 genes, as compared to those from vehicle treatment. Meanwhile, TGF-β3 demonstrated better pathologic recovery process with no obvious necrosis or fracture of collagen fibers. Besides, TGF-β3 revealed a significant reduction of collagen type-III expression in the flexor tendon healing tissues. Conclusion: These findings suggested that TGF-β3 effectively protected against flexor tendon injury via regulating adhesion formation.

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HGF suppresses the production of collagen type III and α-SMA induced by TGF-β1 in healing fibroblasts

European Journal of Applied Physiology ◽

10.1007/s00421-008-0733-7 ◽

2008 ◽

Vol 103 (5) ◽

pp. 489-493 ◽

Cited By ~ 21

Author(s):

Dapeng Jiang ◽

Zhitao Jiang ◽

Fuyou Han ◽

Yubo Zhang ◽

Zhaozhu Li

Keyword(s):

Collagen Type ◽

Collagen Type Iii ◽

Type Iii ◽

Tgf Β1

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Data mining-based study of collagen type III alpha 1 (COL3A1) prognostic value and immune exploration in pan-cancer

Bioengineered ◽

10.1080/21655979.2021.1949838 ◽

2021 ◽

Vol 12 (1) ◽

pp. 3634-3646

Author(s):

Hanyu Zhang ◽

Cheng Ding ◽

Yatong Li ◽

Cheng Xing ◽

Shunda Wang ◽

...

Keyword(s):

Data Mining ◽

Prognostic Value ◽

Collagen Type ◽

Collagen Type Iii ◽

Type Iii ◽

Pan Cancer

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Prognostic value of blood-based fibrosis biomarkers in patients with metastatic colorectal cancer receiving chemotherapy and bevacizumab

Scientific Reports ◽

10.1038/s41598-020-79608-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Neel I. Nissen ◽

Stephanie Kehlet ◽

Mogens K. Boisen ◽

Maria Liljefors ◽

Christina Jensen ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Collagen Type ◽

Performance Status ◽

Drug Uptake ◽

Collagen Type Iii ◽

Serum Samples ◽

Type Iii ◽

Poor Treatment ◽

And Performance

AbstractA desmoplastic colorectal cancer stroma, characterized by excess turnover of the cancer-associated fibroblast derived collagens type III and VI, can lead to reduced drug-uptake and poor treatment response. We investigated the association between biomarkers of collagen type III and VI and overall survival (OS) in patients with metastatic colorectal cancer (mCRC). Serum samples were collected from 252 patients with mCRC prior to treatment with bevacizumab and chemotherapy. Serum concentrations of biomarkers reflecting formation of collagen type III (PRO-C3) and VI (PRO-C6) and degradation of collagen type VI (C6M and C6Mα3) were determined by ELISA. The biomarkers were evaluated for associations with OS, individually, combined, and after adjusting for carcinoembryonic antigen (CEA), lactate dehydrogenase (LDH) and performance status (PS). High baseline levels (> median) of each collagen biomarker were significantly associated with shorter OS (PRO-C3: HR = 2.0, 95%CI = 1.54–2.63; PRO-C6: HR = 1.6, 95%CI = 1.24–2.11; C6M: HR = 1.4, 95%CI = 1.05–1.78; C6Mα3: HR = 1.6, 95%CI = 1.16–2.07). PRO-C3 and PRO-C6 remained significant after adjustment for CEA, LDH and PS. Weak correlations were seen between the collagen biomarkers (r = 0.03–0.59) and combining all improved prognostic capacity (HR = 3.6, 95%CI = 2.30–5.76). Collagen biomarkers were predictive of shorter OS in patients with mCRC. This supports that collagen- and CAF biology is important in CRC.

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