Expressions of Collagen I and III in Hypoxic Keloid Tissue.
BACKGROUND
Wound heals itself spontaneously as physiological process. However, in some individuals, small wounds such as parenteral injections or body piercings may cause increased expression of collagen synthesis. The condition is known as keloid. Histopathology of keloid demonstrates extensive tissue proliferation that extends beyond the margin of primary wound. As a result, it develops uncontrolled or excessive fibrogenesis and tremendous source of collagen that still causes clinical problems until now. A wound, no matter how small the size is, will be followed by increased expression of collagen synthesis. Procollagen I and III is one of markers indicating the development of fibrosis. In fibrosis, there is hypoxia, which is characterized by stabilization of HIF-1α. Therefore, our study was aimed to obtain information about expression of collagen I and III in hypoxic keloid tissue.


METHODS
The study design was observational descriptive. Keloid specimens were obtained from biopsy and preputium skins as the control specimens were obtained from circumcision. There were 10 tissue specimens for each specimen group. The analysis performed were evaluation of mRNA expression on collagen I, collagen III and HIF-1α using RT-PCR, the evaluation of HIF-1α protein level using ELISA and the expression of collagen I and collagen III protein using immunohistochemistry. Statistically, data was analyzed by unpaired t-test.


RESULTS
In keloid with excessive cell proliferation, we found that the expression of procollagen I mRNA increased 35 times and the expression of procollagen III mRNA increased 27.1 times compared to preputium control group (p<0.05). The expression of procollagen I protein in the dermal layer of keloid was 61% and in the preputium was 37% (p<0.05). The expression of collagen III protein in the dermal layer of keloid was 39% and in the preputium was 16% (p<0.05). There was a 5-fold increase on expression of HIF-1α mRNA in keloid tissue compared to those in preputium (p<0.05). The levels of HIF-1α protein in keloid tissue was 0.201 ng/mg protein and the level in preputium was 0.122 ng/mg protein (p<0.05). There was a strong positive and extremely significant correlation between the expression of HIF-1α protein and procollagen III (R=0.744; p<0.05, Pearson), but HIF-1α with procollagen I are weak correlation (R=0.360; p>0.05, Pearson) Conclusion: Expression of collagen I and III have important role in hypoxic keloid tissue characterized by increased expressions. The expression of collagen I and III is associated with stable HIF-1α in keloid tissue.
Biomedical Doctoral Program at Faculty of Medicine, University of Indonesia, Jakarta, Indonesia.|Department of Biochemistry, Faculty of Medicine and Health Sciences of State Islamic University Syarif Hidyatullah, Jakarta, Indonesia.
Endah
E
Wulandari
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia.
Sri Widia A
SW
Jusman
Department of Surgery, Faculty of Medicine, University of Indonesia, Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia.
Yefta
Y
Moenadjat
Department of Histology, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia.
Ahmad A
AA
Jusuf
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia.
Mohamad
M
Sadikin
D024042:Collagen Type I / Q000235:genetics* / Q000378:metabolism*; D024061:Collagen Type III / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D007627:Keloid / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D014945:Wound Healing
D024042:Collagen Type I; D024061:Collagen Type III; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger
HIF-1α; Hypoxia; collagen; keloid