Salamander-Derived, Human-Optimized nAG Protein Suppresses Collagen Synthesis and Increases Collagen Degradation in Primary Human Fibroblasts

被引:15
作者
Al-Qattan, Mohammad M. [1 ,2 ]
Shier, Medhat K. [2 ]
Abd-AlWahed, Mervat M. [2 ]
Mawlana, Ola H. [2 ]
El-Wetidy, Mohammed S. [2 ]
Bagayawa, Reginald S. [2 ]
Ali, Hebatallah H. [2 ]
Al-Nbaheen, May S. [3 ]
Aldahmash, Abdullah M. [3 ,4 ,5 ]
机构
[1] King Saud Univ, Dept Surg, Riyadh, Saudi Arabia
[2] King Saud Univ, Coll Med, Res Ctr, Riyadh 11461, Saudi Arabia
[3] King Saud Univ, Coll Med, Dept Anat, Stem Cell Unit, Riyadh 11461, Saudi Arabia
[4] Odense Univ Hosp, Endocrine Res Lab KMEB, DK-5000 Odense, Denmark
[5] Univ Southern Denmark, Odense, Denmark
关键词
GROWTH-FACTOR-BETA; LIMB REGENERATION; NERVE DEPENDENCE; DISEASE; FIBROSIS; MECHANISMS; MATRIX; REPAIR;
D O I
10.1155/2013/384091
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 [微生物学]; 090105 [作物生产系统与生态工程];
摘要
Unlike humans, salamanders regrow their amputated limbs. Regeneration depends on the presence of regenerating axons which upregulate the expression of newt anterior gradient (nAG) protein. We had the hypothesis that nAG might have an inhibitory effect on collagen production since excessive collagen production results in scarring, which is a major enemy to regeneration. nAG gene was designed, synthesized, and cloned. The cloned vector was then transfected into primary human fibroblasts. The results showed that the expression of nAG protein in primary human fibroblast cells suppresses the expression of collagen I and III, with or without TGF-beta 1 stimulation. This suppression is due to a dual effect of nAG both by decreasing collagen synthesis and by increasing collagen degradation. Furthermore, nAG had an inhibitory effect on proliferation of transfected fibroblasts. It was concluded that nAG suppresses collagen through multiple effects.
引用
收藏
页数:9
相关论文
共 32 条
[1]
Hypertrophic scar formation following burns and trauma: New approaches to treatment [J].
Aarabi, Shahram ;
Longaker, Michael T. ;
Gurtner, Geoffrey C. .
PLOS MEDICINE, 2007, 4 (09) :1464-1470
[2]
Fragments of extracellular matrix as mediators of inflammation [J].
Adair-Kirk, Tracy L. ;
Senior, Robert M. .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2008, 40 (6-7) :1101-1110
[3]
Factors in the pathogenesis of Dupuytren's contracture [J].
Al-Qattan, Mohammad M. .
JOURNAL OF HAND SURGERY-AMERICAN VOLUME, 2006, 31A (09) :1527-1534
[4]
Uniaxial strain upregulates matrix-degrading enzymes produced by human vascular smooth muscle cells [J].
Asanuma, K ;
Magid, R ;
Johnson, C ;
Nerem, RM ;
Galis, ZS .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2003, 284 (05) :H1778-H1784
[5]
Mechanisms of disease:: Role of transforming growth factor β in human disease. [J].
Blobe, GC ;
Schiemann, WP ;
Lodish, HF .
NEW ENGLAND JOURNAL OF MEDICINE, 2000, 342 (18) :1350-1358
[6]
Appendage regeneration in adult vertebrates and implications for regenerative medicine [J].
Brockes, JP ;
Kumar, A .
SCIENCE, 2005, 310 (5756) :1919-1923
[7]
Amphibian limb regeneration: Rebuilding a complex structure [J].
Brockes, JP .
SCIENCE, 1997, 276 (5309) :81-87
[8]
Brown PT, 2013, CURR PHARM DESIGN, V19, P3429
[9]
Treatment of Idiopathic Pulmonary Fibrosis with Losartan: A Pilot Project [J].
Couluris, Marisa ;
Kinder, Brent W. ;
Xu, Ping ;
Gross-King, Margaret ;
Krischer, Jeffrey ;
Panos, Ralph J. .
LUNG, 2012, 190 (05) :523-527
[10]
Coronary perivascular fibrosis is associated with impairment of coronary blood flow in patients with non-ischemic heart failure [J].
Dai, Zhehao ;
Fukumoto, Yoshihiro ;
Shimokawa, Hiroaki .
JOURNAL OF CARDIOLOGY, 2012, 60 (5-6) :416-421