Metabolism of the aminoterminal propeptide of type III procollagen in cultures of human proximal tubular cells.
Degradation of the intact form of the aminoterminal propeptide of type III procollagen (PIIINP) has been established in the liver, whereas the col 1 domain of PIIINP is extracted by the kidneys. We used native human PIIINP and col 1 domain of PIIINP to investigate the degradation of PIIINP in cultures of human proximal tubular cells. Normal renal tissue was obtained from the healthy part of kidneys surgically removed and from biopsies from a total of 10 patients. The degradation was characterized by incubation of [125I]-PIIINP followed by gel filtration. We found that in physiological concentrations (4.4 micrograms l-1 and 11.9 micrograms l-1 intact PIIINP was almost totally degraded, but not col 1 domain. High concentrations of PIIINP (20-50 micrograms l-1) had a non-linear, non-monoexponential degradation over time, which suggests several steps. Gel filtration of [125I]-PIIINP after 1 h, 3 h, 6 h and 24 h of incubation confirmed the observation by showing the rapid formation of a high-molecular-weight fraction, followed by the slower formation of a low-molecular-weight fraction. The high-molecular-weight fraction was PIIINP immunoreactive, but not the low-molecular-weight fraction. We conclude that cultures of human proximal tubular cells degrade intact human PIIINP by the formation of high- and low-molecular-weight fractions. Earlier findings that extraction of the PIIINP col 1 domain takes place in the kidneys, cannot be explained by degradation by the proximal tubular cells.
Jensen
L T
LT
Department of Rheumatology, Hvidovre Hospital, University of Copenhagen.
Blaehr
H
H
Andersen
C B
CB
Risteli
J
J
Lorenzen
I
I
D002478:Cells, Cultured; D002850:Chromatography, Gel; D006801:Humans; D007124:Immunoenzyme Techniques; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D011347:Procollagen / Q000378:metabolism*
D010446:Peptide Fragments; D011347:Procollagen; C041876:procollagen Type III-N-terminal peptide