Parietal epithelial cell dysfunction in crescentic glomerulonephritis

Crescentic glomerulonephritis represents a group of kidney diseases characterized by rapid loss of kidney function and the formation of glomerular crescents. While the role of the immune system has been extensively studied in relation to the development of crescents, recent findings show that parietal epithelial cells play a key role in the pathophysiology of crescent formation, even in the absence of immune modulation. This review highlights our current understanding of parietal epithelial cell biology and the reported physiological and pathological roles that these cells play in glomerular lesion formation, especially in the context of crescentic glomerulonephritis.

Effect of Glutamine on Apoptosis-inducing Factor Expression and Apoptosis of Glomerular Parietal Epithelial Cells of Cisplatin-exposed Rats

AIM: This study analyzed the nephroprotective effect by examining apoptosis-inducing factor (AIF) expression and apoptosis rate in the glomerular parietal epithelial cell of cisplatin-exposed rats. METHODS: Samples consisted of 30 rats (divided into 3 groups: Group P0 received no treatment, group P1 received a cisplatin injection on the 7th day, and group P2 received glutamine injection on days 1–7 and cisplatin injection on the 7th day). After 72 h, the tissue samples were immunohistochemically processed. AIF expression was measured in an Allred score. The apoptosis rate was measured in apoptotic cells/field of view. Statistical analysis was carried out using JASP Statistics ver. 0.12.0 (p < 0.05). RESULTS: AIF expression values are follows: P0 = 4.89 ± 0.418, P1 = 6.14 ± 0.685, and P2 = 4.95 ± 0.530. The Kruskal–Wallis test result showed a significant difference (p < 0.05) between the groups and Dunn’s post hoc test showed a significant difference between P0 and P1 and between P1 and P2, but no significant difference between P0 and P2. Meanwhile, apoptosis rate values are as follows: P0 = 24.3 ± 9.821, P1 = 123.6 ± 16.008, and P2 = 77.2 ± 10.644. The Kruskal–Wallis test result showed a significant difference (p < 0.05) between the groups, and Dunn’s post hoc test showed a significant difference between P0 and P1, between P1 and P2, and between P0 and P2. CONCLUSION: The expression of AIF and apoptosis of glomerular parietal epithelial cells of the cisplatin-exposed rat has decreased after glutamine treatment.

Castrated autoimmune glomerulonephritis mouse model shows attenuated glomerular sclerosis with altered parietal epithelial cell phenotype

Sex hormones help in maintaining proper immunity as well as renal homeostasis in mammals, and these multi-functional properties characterize the onset of sex-dependent diseases. To clarify the contribution of sex hormones to autoimmune disease-related renal pathogenesis, BXSB/MpJ- Yaa was investigated as a murine autoimmune glomerulonephritis model. BXSB/MpJ- Yaa and its wild-type, BXSB/MpJ- Yaa+ were castrated or sham-operated at three weeks and examined until six months of age. Both castrated strains showed significantly lower serum testosterone levels and body weights than sham-operated mice. Castration did not change the disease phenotypes in BXSB/MpJ- Yaa+. At three months, both sham-operated and castrated BXSB/MpJ- Yaa manifested splenomegaly, autoantibody production, and glomerulonephritis, and castrated BXSB/MpJ- Yaa tended to show heavier spleen weights than the sham-operated group. At six months, both the treated BXSB/MpJ- Yaa showed equivalent autoimmune disease conditions; however, castrated mice clearly showed milder glomerular sclerotic lesions than the sham-operated groups. Urinary albumin excretion in castrated BXSB/MpJ- Yaa was significantly milder than in sham-operated mice at four months, but those of both the treated BXSB/MpJ- Yaa were comparable at six months. The examined renal histopathological indices in parietal epithelial cells were remarkably altered by castration. Briefly, castration decreased the height of parietal epithelial cells and total parietal epithelial cell number in BXSB/MpJ- Yaa at six months. For immunostaining, parietal epithelial cells facing the injured glomeruli of BXSB/MpJ- Yaa expressed CD44, an activated parietal epithelial cell marker, and CD44-positive parietal epithelial cells showed nuclear localization of the androgen receptor and proliferation marker Ki67. CD44- or Ki67-positive parietal epithelial cells were significantly fewer in castrated group than in sham-operated BXSB/MpJ- Yaa at six months. Further, quantitative indices for CD44-positive parietal epithelial cell number and frequency in renal corpuscles positively correlated with glomerular sclerotic severity in BXSB/MpJ- Yaa. In conclusion, androgen seemed to have an effect on both systemic immunity and renal morpho-function; however, the effect on the latter could be more clearly observed in BXSB/MpJ- Yaa, as parietal epithelial cell activation resulted in glomerular sclerosis.