Elevated prolidase activity in keloids: correlation with type I collagen turnover.
BACKGROUND
Keloid pathogenesis involves an altered balance of extracellular matrix metabolism, mainly accumulation of type I collagen. This could be due to excessive synthesis or decreased degradation of matrix, or a combination of both processes. Prolidase, an imidodipeptide-cleaving cytosolic enzyme, plays an important role in the collagen catabolic process by recycling proline for collagen synthesis. Collagen accumulation in keloids is due to an imbalance in the steady state of collagen turnover.


OBJECTIVE
To investigate prolidase activity and its role in the steady state of collagen turnover between normal skin and keloid tissue and their derived fibroblasts.


METHODS
Ten sets of keloid and normal skin tissues and their derived fibroblasts were employed. Measurements were made of tissue prolidase activity, free proline level, and concentrations of the collagen synthesis product aminoterminal propeptide of type I procollagen (PINP) and the collagen degradative product carboxyterminal telopeptide of type I collagen (ICTP). Also, synthesis of collagens type I and III and matrix metalloproteinases 1 and 2 was investigated using Western blot analysis.


RESULTS
Keloid tissues had a significant increase in prolidase activity, up to fourfold that in normal skin. The elevated prolidase activity was accompanied by an increase in tissue PINP and ICTP concentrations in keloid; in addition, the collagen turnover index (PINP/ICTP) was higher in keloids.


CONCLUSIONS
The combination of elevated prolidase activity and associated higher collagen synthesis to degradation ratio in keloids suggests a possible metabolic process for the excessive accumulation of type I collagen in keloids.
Duong
H S
HS
Division of Oral Biology and Medicine, University of California Los Angeles, School of Dentistry, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
Zhang
Q-Z
QZ
Le
A D
AD
Kelly
A P
AP
Kamdar
R
R
Messadi
D V
DV
D000293:Adolescent; D000328:Adult; D002477:Cells; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism*; D017077:Culture Media, Conditioned; D004150:Dipeptidases / Q000235:genetics / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D007627:Keloid / Q000201:enzymology* / Q000378:metabolism; D008875:Middle Aged; D011392:Proline / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012867:Skin / Q000201:enzymology / Q000378:metabolism
D024042:Collagen Type I; D017077:Culture Media, Conditioned; D012333:RNA, Messenger; D003094:Collagen; D011392:Proline; D004150:Dipeptidases; C022449:proline dipeptidase