Compensatory Renal Growth in Uninephrectomized Immature Rats: Proliferative Activity and Epidermal Growth Factor

Abstract

ABSTRACT. Compensatory response to uninephrectomy in immature animals is stronger compared with that in adult ones and the response is due mainly to renal cell proliferation. The present study explored to show the growth pattern of the remaining kidney immediately after uninephrectomy in immature rats with special reference to proliferating activity and epidermal growth factor (EGF). Immunolocalizations of proliferating cell nuclear antigen (PCNA) and EGF in immature rat kidney were examined during the first three days after uninephrectomy. Semi-quantitative analysis of the expression of preproEGF mRNA was performed. One day after the operation, the PCNA positive cell ratios in the glomeruli and the proximal tubules were significantly higher in unilaterally nephrectomized (UNx) rats than in sham-operated (Sham) rats. In UNx and Sham rats, the proximal and distal tubular cells showed positive reactions to EGF antibody. The positive reaction of proximal tubules to EGF antibody was weaker in UNx than in Sham rats 1 day after the operation, while the degree of reactivity was not different between UNx and Sham rats 3 days after the operation. The level of expression of preproEGF mRNA in the kidney was significantly lower in UNx than in Sham rats 1 day after the operation. These results indicate that unilateral nephrectomy in immature rats causes increased proliferative activity and decreased expression of EGF in the remaining kidney during the early period of compensatory renal growth.KEY WORDS: EGF, glomerulus, PCNA, proximal tubules, uninephrectomy.J. Vet. Med. Sci. 72(8): 975-980, 2010 Compensatory renal growth after unilateral nephrectomy has been intensely investigated [5,12,18] and includes cellular hypertrophy, hyperplasia, and apoptosis [30]. In immature animals, the compensatory response to uninephrectomy is stronger than in adult ones [6]. The response is largely due to hyperplasia in immature animals, and due to hypertrophy in adult animals [8]. On the other hand, a variety of polypeptide growth factors regulate cell proliferation during development [1]. Of these growth factors, epidermal growth factor (EGF) was first isolated from mouse submandibular glands [4]. The kidney is the organ next to the salivary glands in secreting a large amount of EGF [11]. EGF is involved in the process of preventing renal tubular scarring in 5/6 nephrectomized immature rats by protein restriction [17]. Addition of EGF to renal organ culture medium causes an increased uptake of bromodeoxyuridine (BrdU) [26]. Absence of EGF in the conditions after acute renal failure, where its mitogenic properties would be most appropriate, suggests that the EGF of renal origin is not acting as a mitogen during kidney regeneration [20]. Recently, we have reported that EGF plays an important role in both cell proliferation and maturation of the proximal tubules in perinatal rat kidney [23]. These findings lead us to expect that some changes in proliferative activity and localization of the growth factor would be occurred in the remaining k...

Comprehensive expression analysis of mRNA and microRNA for the investigation of compensatory mechanisms in the rat kidney after unilateral nephrectomy

“…Sex and age differences in compensatory mechanisms in the kidney have been reported in several studies. For example, after UNx, hypertrophy occurs in the residual kidneys of adult male rats, whereas hyperplasia occurs in young male and female rats, suggesting that sexual hormones are involved in these differences (Azurmendi et al, 2013;Mulroney et al, 1991;Mulroney et al, 1996;Mulroney et al, 1999;Mulroney, Lumpkin, et al, 1992;Mulroney & Pesce, 2000;Okada et al, 2010;Sun et al, 2006;Tovar et al, 1995). Additionally, both male and female rats used in repeateddose toxicity studies are sexually mature at least at the end of the experiment.…”

“…Based on previous findings that there are age-and sex-related differences in these mechanisms (Azurmendi et al, 2013;Mulroney et al, 1996;Mulroney, Haramati, Roberts, & LeRoith, 1991;Mulroney, Lumpkin, Roberts, LeRoith, & Haramati, 1992;Mulroney & Pesce, 2000;Mulroney, Woda, Johnson, & Pesce, 1999;Okada et al, 2010;Sun, Langer, Devish, & Lane, 2006;Tovar, Sanchez-Capelo, Cremades, & Penafiel, 1995), the mode of action of compensation in the kidney can vary depending on the experimental conditions. Thus, comprehensive analysis in male and female adult rats, which are widely used in toxicity tests, is considered useful for application in chemical risk assessment.…”

Epidermal growth factor, from gene organization to bedside

“…Similar to other members in the EGF family, EGF detected in biological and pathological states exhibits different levels of expression [37–39]. Its expression levels also vary at different stages of development [40–42].…”