Paracrine Effects of Renal Proximal Tubular Epithelial Cells on Podocyte Injury under Hypoxic Conditions Are Mediated by Arginase-II and TGF-β1

Ma, Yiqiong; Potenza, Duilio Michele; Ajalbert, Guillaume; Brenna, Andrea; Zhu, Cui; Ming, Xiu‐Fen; Yang, Zhihong

doi:10.3390/ijms24043587

Cited by 4 publications

(1 citation statement)

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“…Immunofluorescence staining was performed as previously described [ 41 ]. Briefly, the kidneys of both male and female wt and arg-ii −/− mice ( n = 10 mice per group) were isolated, fixed with 4% paraformaldehyde (pH 7.0), and eventually embedded in paraffin.…”

Section: Methodsmentioning

confidence: 99%

Elevation of Arginase-II in Podocytes Contributes to Age-Associated Albuminuria in Male Mice

Ajalbert

Brenna

Ming

et al. 2023

IJMS

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One of the manifestations of renal aging is podocyte dysfunction and loss, which are associated with proteinuria and glomerulosclerosis. Studies show a male bias in glomerular dysfunction and chronic kidney diseases, and the underlying mechanisms remain obscure. Recent studies demonstrate the role of an age-associated increase in arginase-II (Arg-II) in proximal tubules of both male and female mice. However, it is unclear whether Arg-II is also involved in aging glomeruli. The current study investigates the role of the sex-specific elevation of Arg-II in podocytes in age-associated increased albuminuria. Young (3–4 months) and old (20–22 months) male and female mice of wt and arginase-II knockout (arg-ii−/−) were used. Albuminuria was employed as a readout of glomerular function. Cellular localization and expression of Arg-II in glomeruli were analyzed using an immunofluorescence confocal microscope. A more pronounced age-associated increase in albuminuria was found in male than in female mice. An age-associated induction of Arg-II in glomeruli and podocytes (as demonstrated by co-localization of Arg-II with the podocyte marker synaptopodin) was also observed in males but not in females. Ablation of the arg-ii gene in mice significantly reduces age-associated albuminuria in males. Also, age-associated decreases in podocyte density and glomerulus hypertrophy are significantly prevented in male arg-ii−/− but not in female mice. However, age-associated glomerulosclerosis is not affected by arg-ii ablation in both sexes. These results demonstrate a role of Arg-II in sex-specific podocyte injury in aging. They may explain the sex-specific differences in the development of renal disease in humans during aging.

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Section: Methodsmentioning

confidence: 99%