Do extraglomerular microvasculature and mesenchymal interstitial cell proliferation indicate a stable course of lupus nephritis?

Autoradiography with [3H]thymidine and electron microscopy were used to determine (a) the patterns of cellular division exhibited by intact anemones, (b) if measurable increases in cellular proliferation accompany oral-disc regeneration, (c) whether interstitial cells are present in Aiptasia, and (d) if these cells could be responsible for the latter proliferative patterns. An oral-aboral gradient in cellular proliferation was exhibited by the epidermis of uncut anemones, with the highest levels in the tentacles. Wound healing did not require cell proliferation and did not immediately stimulatecellular division which was associated with subsequent morphogenetic events. Indices of presumptive oral-disc [3H]thymidine uptake into nuclei increased tenfold with the outgrowth of the new tentacles. This increase occurred in the epidermis, while only small amounts of gastrodermal proliferation were detected. It is hypothesized that the epidermis contributes new cells to the expanding gastrodermis during tentacle budding. Most of the [3H]thymidine-labeled nuclei were localized in the basal portions of the epidermis of intact anemones and 1- to 2-day-old regenerates; very few gastrodermal nuclei accumulated the label. Nests of interstitial cells and transforming interstitial cells were localized in the exact epidermal regions where nuclear labeling took place, suggesting that the proliferative patterns of intact and regenerating Aiptasia are a function of their interstitial cell distribution.

Download Full-text

Cyclin kinase inhibitor p21CIP1/WAF1 limits interstitial cell proliferation following ureteric obstruction

AJP Renal Physiology ◽

10.1152/ajprenal.1999.277.6.f948 ◽

1999 ◽

Vol 277 (6) ◽

pp. F948-F956 ◽

Cited By ~ 10

Author(s):

Jeremy Hughes ◽

Paul Brown ◽

Stuart J. Shankland

Keyword(s):

Cell Proliferation ◽

Epithelial Cell ◽

Interstitial Cell ◽

Tubular Epithelial Cell ◽

Collagen I ◽

Macrophage Infiltration ◽

Nuclear Antigen ◽

Epithelial Cell Proliferation ◽

Ureteric Obstruction ◽

Proliferation And Apoptosis

Tubulointerstitial renal injury induced by unilateral ureteric obstruction (UUO) is characterized by marked cell proliferation and apoptosis. Proliferation requires cell cycle transit that is positively regulated by cyclins and cyclin-dependent kinases (CDKs) and inhibited by the CIP/KIP family of cyclin-dependent kinase inhibitors (CKIs: p21, p27, and p57). We have shown that the absence of p27 results in markedly increased tubular epithelial cell proliferation and apoptosis following UUO (V. Ophascharoensuk, M. L. Fero, J. Hughes, J. M. Roberts, and S. J. Shankland. Nat. Med.4: 575–580, 1998). Since p21 mRNA is upregulated following UUO, we hypothesized that p21 would also serve to limit cell proliferation and apoptosis. We performed UUO in p21 +/+ and p21 −/− mice. Cell proliferation [bromodeoxyuridine (BrdU), proliferating cell nuclear antigen (PCNA)], apoptosis [terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method], interstitial myofibroblast accumulation (actin), macrophage infiltration (F4/80), and collagen I expression were quantified at days 3, 7, and 14. In contrast to p27 −/− mice, there was no difference in tubular epithelial cell proliferation or apoptosis between p21 −/− and p21 +/+ mice at any time point. However, interstitial cell proliferation at day 3 was significantly increased in p21 −/− mice [BrdU, 40.7 ± 1.9 cells/high-power field (cells/hpf) vs. 28.8 ± 2, P< 0.005], although, interestingly, no difference was seen in interstitial cell apoptosis. Actin/BrdU double staining demonstrated increased interstitial myofibroblast proliferation at day 3 in p21 −/− animals (10 ± 0.12 vs. 5.8 ± 0.11 cells/hpf, P < 0.05), which was followed by increased myofibroblast accumulation at day 7 in p21 −/− mice. No differences were detected in interstitial macrophage infiltration, collagen I deposition or transforming growth factor-β1 mRNA (in situ hybridization) expression. In conclusion p21, unlike p27, is not essential for the regulation of tubular epithelial cell proliferation and apoptosis following UUO, but p21 levels do serve to limit the magnitude of the early myofibroblast proliferation. This study demonstrates a differential role for the CKI p21 and p27 in this model.

Download Full-text