Ultraviolet irradiation induces thrombospondin-1 which attenuates type I procollagen downregulation in human dermal fibroblasts.
BACKGROUND
Thrombospondin-1 (TSP-1) is a matricellular glycoprotein and recognized as an inhibitor of angiogenesis and an activator of transforming growth factor-beta (TGF-beta). Although TSP-1 expression has been shown to be regulated by various stimuli including UV in some types of cell, more work need to be done to understand the regulation of TSP-1 expression and its functional significances in many other types of cell.


OBJECTIVE
In this study, we investigated the effect of UV on TSP-1 expression in human skin dermis and dermal fibroblasts and the role of TSP-1 on the type I procollagen expression after UV exposure.


METHODS
Human buttock skin and human dermal fibroblasts were irradiated with UV. The mRNA and the protein levels of TSP-1 or type I procollagen were measured by real-time polymerase chain reaction and Western blotting, respectively.


RESULTS
We found that UV irradiation increased TSP-1 expression at the mRNA and protein levels in human skin dermis and dermal fibroblasts. UV-induced TSP-1 expression was greatly suppressed by inhibition of the PI3K, Akt, or mTOR pathways. The inhibition of TSP-1 activity by a blocking peptide or suppression of TSP-1 expression by specific TSP-1 small interfering RNA augmented the UV-induced decrease of type I procollagen expression.


CONCLUSIONS
Our results suggest that UV-induced TSP-1 plays an important role on alleviating and/or recovering the type I procollagen expression downregulated by UV in human dermal fibroblasts.
Seo
Jo-Eun
JE
Department of Dermatology, Seoul National University College of Medicine, and Laboratory of Cutaneous Aging Research, Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
Kim
Sangmin
S
Shin
Mi Hee
MH
Kim
Mi-Sun
MS
Eun
Hee Chul
HC
Park
Chi-Hyun
CH
Chung
Jin Ho
JH
D000328:Adult; D024042:Collagen Type I / Q000032:analysis / Q000378:metabolism*; D015536:Down-Regulation; D005347:Fibroblasts / Q000737:chemistry / Q000378:metabolism / Q000528:radiation effects*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D012867:Skin / Q000737:chemistry / Q000378:metabolism / Q000528:radiation effects*; D058570:TOR Serine-Threonine Kinases; D019700:Thrombospondin 1 / Q000032:analysis / Q000378:metabolism*; D014466:Ultraviolet Rays
D024042:Collagen Type I; D047908:Intracellular Signaling Peptides and Proteins; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger; D019700:Thrombospondin 1; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases