METABOLISM OF THE AMINOTERMINAL PROPEPTIDE OF TYPE-III PROCOLLAGEN INCULTURES 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 t he 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 t issue was obtained from the healthy part of kidneys surgically removed and from biopsies from a total of 10 patients. The degradation was ch aracterized by incubation of [I-125]-PIIINP followed by gel filtration . We found that in physiological concentrations (4.4-mu-g l-1 and 11.9 -mu-g l-1) intact PIIINP was almost totally degraded, but not col 1 do main. High concentrations of PIIINP (20-50-mu-g l-1) had a non-linear, non-monoexponential degradation over tinic, which suggests several st eps. Gel filtration of [I-125]-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 w as PIIINP immunoreactive, but not the low-molecular-weight fraction. W e conclude that cultures of human proximal tubular cells degrade intac t human PIIINP by the formation of high- and low-molecular-weight frac tions. Earlier findings that extraction of the PIIINP col 1 domain tak es place in the kidneys, cannot he explained by degradation by the pro ximal tubular cells.