Figure 8.

Kidney collagen synthesis rates in Mrc2^+/+ and Mrc2^−/− mice after UUO. (A) Interstitial collagens I and III are dramatically upregulated in CKD as reflected by kidney procollagen mRNA levels measured by qPCR relative to 18S levels using samples that were pooled from five individual wild-type mice at each time-point after UUO surgery. Kidney procollagen I (α1) (B) but not procollagen III (α1) (C) levels were significantly higher in the Mrc2^−/− mice 14 and 21 days after UUO. These data are shown as mean relative expression levels corrected to 18S ± SD, using groups of 10 individual mice at each time point. A separate cohort of mice was continuously labeled with deuterated water after the UUO procedure (n=3 per group) and the level of deuterium incorporation into stable C-H bonds of hydroxyproline was measured by gas chromatography/mass spectroscopy to calculate the accumulation of newly synthesized collagen in the obstructed and contralateral (contra) kidneys. Total kidney collagen was confirmed to be significantly higher in this new cohort of Mrc2^−/− mice (D), but the fractional collagen synthesis was similar in Mrc2^+/+ and Mrc2^−/− mice when measured on day 14 after UUO (E). Results for the contralateral (contra) nonobstructed kidneys show no differences in total collagen and fractional new collagen between the genotypes. ^†P<0.05 for Mrc2^−/− versus Mrc2^+/+ Contra and UUO groups.