A New Method to Measure Type I and III Collagen Synthesis in Human Skin In Vivo: Demonstration of Decreased Collagen Synthesis After Topical Glucocorticoid Treatment

Oikarinen, Aarne; Autio, Pekka; Kiistala, U; Risteli, Leila; Risteli, Juha

doi:10.1111/1523-1747.ep12555884

Cited by 86 publications

(65 citation statements)

References 21 publications

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“…Several studies have indicated that the skin synthesis of type I and III collagens is tightly co-regulated (Oikarinen et al, 1992;Autio et al, 1994). In addition, the present results indicate that type III collagen synthesis accounts for about 22% of the total skin synthesis of type I and III collagens, irrespective of the radiation therapy, which is consistent with previous estimates in physiological conditions (Autio et al, 1994).…”

Section: Discussionsupporting

confidence: 92%

“…As the procollagen propeptides are cleaved off in extracellular matrix into the interstitial fluid when a collagen molecule is formed , it is possible to measure the actual collagen synthesis in skin by measuring the concentrations of the propeptides in interstitial fluid (Oikarinen et al, 1992). The concentrations of PICP and PINP, and PIIINP, respectively, have been shown to indicate the local ongoing synthesis of type I and type III collagen in dermis (Oikarinen et al, 1992;Autio et al, 1994Autio et al, , 1996.…”

Section: Discussionmentioning

confidence: 99%

“…The concentrations of PICP and PINP, and PIIINP, respectively, have been shown to indicate the local ongoing synthesis of type I and type III collagen in dermis (Oikarinen et al, 1992;Autio et al, 1994Autio et al, , 1996. The synthesis of procollagens slowly decreases with age, being most obvious after the seventh decade.…”

Section: Discussionmentioning

confidence: 99%

“…Here, we used a sensitive, direct and non-invasive method, based on the use of the suction blister technique (Kiistala, 1968) and on the radioimmunoassays of procollagen propeptides (Risteli et al, 1988;Melkko et al, 1990Melkko et al, , 1996 to study local ongoing type I and III collagen synthesis (Oikarinen et al, 1992) in the irradiated and unirradiated skin of breast cancer patients 1-5 years after the radiation therapy. (Risteli et al, 1988;Melkko et al, 1990Melkko et al, , 1996.…”

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confidence: 99%

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Demonstration of increased collagen synthesis in irradiated human skin in vivo

Autio

Saarto²,

Tenhunen³

et al. 1998

Br J Cancer

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Summary Fibrosis is a common side-effect of radiation therapy. As a complex network of cytokines and other mediators plays a central role in the process leading to fibrosis, we used an in vivo method to measure skin collagen synthesis, taking into account the physiological conditions. We determined suction blister (i.e. interstitial) fluid concentrations of types and IlIl procollagen propeptides, reflecting types I and Ill collagen synthesis, in irradiated and unirradiated skin of breast cancer patients 1-5 years after surgery and radiation therapy, hence using the patients as their own controls. The mean concentrations of the measured collagen markers were approximately two times higher in the irradiated skin than in the unirradiated contralateral breast skin. The difference slowly diminishes with time. These results indicate that abundant collagen synthesis in the irradiated skin continues several years after discontinuation of the radiation therapy, leading to fibrosis.The method outlined here offers a new in vivo perspective to study events leading to radiation fibrosis.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Demonstration of increased collagen synthesis in irradiated human skin in vivo

Autio

Saarto²,

Tenhunen³

et al. 1998

Br J Cancer

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“…Supernatants were collected and ultrafiltered (Centriprep-50 columns, Amicon), and 200 L of the retentate was taken for analysis in a PICP RIA kit (Orion Diagnostica). We used the sequential saturation procedure as described by Oikarinen et al 19 to increase the sensitivity of the assay. We also measured urinary PICP concentration using the abovedescribed kit.…”

Section: Evaluation Of Collagen I Synthesismentioning

confidence: 99%

Vascular Endothelin-1 Gene Expression and Synthesis and Effect on Renal Type I Collagen Synthesis and Nephroangiosclerosis During Nitric Oxide Synthase Inhibition in Rats

et al. 1999

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Background-The progression of hypertension during NO deficiency is associated with renal vascular fibrosis due to increased extracellular matrix (mainly collagen I) formation. The purpose of the present study was to investigate whether endothelin-1 (ET-1) is involved in this pathophysiological process. Methods and Results-Treatment of rats for 4 weeks with the NO synthase inhibitor N -nitro-L-arginine methyl ester (L-NAME) 50 mg ⅐ kg Ϫ1 ⅐ d Ϫ1 increased systolic blood pressure to 159Ϯ12 mm Hg. In animals treated with L-NAME, histological evaluation of renal sections revealed an increased formation of extracellular matrix (Masson's trichrome), and specifically of collagens (Sirius red). A part of this fibrosis was attributed to abnormal collagen I presence, because mRNA expression of the collagen I ␣1 chain (reverse transcription-polymerase chain reaction) and procollagen I formation (radioimmunoassay) were increased 3-and 2.5-fold, respectively, in the renal resistance vessels of hypertensive animals. In subsequent experiments, we examined whether ET-1 was involved in activation of collagen I formation. mRNA expression (RNase protection assay) of preproET-1 and ET-1 content (radioimmunoassay) were 10-fold and 3-fold increased, respectively, in renal microvessels of rats treated with L-NAME. Interestingly, in these vessels, ET-1 (immunostaining) was colocalized with sudanophilic lesions. Bosentan, an ET receptor antagonist (20 mg, coadministered with L-NAME canceled the increased mRNA expression and synthesis of collagen I and attenuated the severity of renal vascular lesions without affecting L-NAME-induced high blood pressure. Conclusions-These data demonstrate that ET-1 synthesis is increased in renal microvessels when NO production is suppressed. In this model of hypertension, ET-1 is a major activator of collagen I formation in renal resistance vessels and participates in the development of renal fibrosis without affecting systolic blood pressure. (Circulation. 1999;99:2185-2191.)

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