In:
PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 6 ( 2021-6-7), p. e0252758-
Abstract:
Angiotensin-converting enzyme 2 (ACE2) has been implicated in the pathogenesis of experimental kidney disease. ACE2 is on the X chromosome, and in mice, deletion of ACE2 leads to the development of focal segmental glomerulosclerosis (FSGS). The relationship between sex and renal ACE2 expression in humans with kidney disease is a gap in current knowledge. Methods We studied renal tubulointerstitial microarray data and clinical variables from subjects with FSGS enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) study. We compared relationships between ACE2 expression and age, estimated glomerular filtration rate (eGFR), urinary albumin to creatinine ratio (UACR), interstitial fibrosis, tubular atrophy, and genes implicated in inflammation and fibrosis in male and female subjects. Results ACE2 mRNA expression was lower in the tubulointerstitium of males compared to females ( P = 0.0026). Multiple linear regression analysis showed that ACE2 expression was related to sex and eGFR but not to age or treatment with renin angiotensin system blockade. ACE2 expression is also related to interstitial fibrosis, and tubular atrophy, in males but not in females. Genes involved in inflammation ( CCL2 and TNF ) correlated with ACE2 expression in males ( TNF : r = -0.65, P 〈 0.0001; CCL2 : r = -0.60, P 〈 0.0001) but not in females. TGFB1, a gene implicated in fibrosis correlated with ACE2 in both sexes. Conclusions Sex is an important determinant of ACE2 expression in the tubulointerstitium of the kidney in FSGS. Sex also influences the relationships between ACE2, kidney fibrosis, and expression of genes involved in kidney inflammation.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0252758
DOI:
10.1371/journal.pone.0252758.g001
DOI:
10.1371/journal.pone.0252758.g002
DOI:
10.1371/journal.pone.0252758.g003
DOI:
10.1371/journal.pone.0252758.g004
DOI:
10.1371/journal.pone.0252758.g005
DOI:
10.1371/journal.pone.0252758.g006
DOI:
10.1371/journal.pone.0252758.g007
DOI:
10.1371/journal.pone.0252758.g008
DOI:
10.1371/journal.pone.0252758.g009
DOI:
10.1371/journal.pone.0252758.g010
DOI:
10.1371/journal.pone.0252758.g011
DOI:
10.1371/journal.pone.0252758.t001
DOI:
10.1371/journal.pone.0252758.t002
DOI:
10.1371/journal.pone.0252758.t003
DOI:
10.1371/journal.pone.0252758.t004
DOI:
10.1371/journal.pone.0252758.t005
DOI:
10.1371/journal.pone.0252758.s001
DOI:
10.1371/journal.pone.0252758.s002
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2267670-3
Permalink