Glomerulosclerosis and Tubulointerstitial Fibrosis are Attenuated with 17β-Estradiol in the Aging Dahl Salt Sensitive Rat

Christine Maric, Kathryn Sandberg, Carmen Hinojosa‐Laborde
In: Journal of the American Society of Nephrology · 2004 · vol. 15(6) , pp. 1546–1556 · doi:10.1097/01.asn.0000128219.65330.ea · PMID:15153565 · W2119218375
article OA: closed CC0 ⤵ 1 in-corpus citation
View on OpenAlex View on PubMed View at publisher

Abstract

This study examined the effects of estrogen deficiency by ovariectomy (OVX) and 17beta-estradiol (E(2)) replacement (OVX+E(2)) on glomerulosclerosis and tubulointerstitial fibrosis and the mechanisms contributing to these changes, including expression of collagen type IV and laminin, transforming growth factor-beta (TGF-beta), and activity of matrix metalloproteinases (MMP) in the kidneys of young (4 mo [4M]) and aged (12 mo [12M]) Dahl salt-sensitive (DSS) rats maintained on a low-salt (0.1% NaCl) diet. While normal renal morphology was observed in the 4M rats in all treatment groups, moderate to severe glomerulosclerosis (glomerulosclerotic index [GSI]: 4M, 0.22 +/- 0.09 versus 12M, 1.43 +/- 0.17; P < 0.001) and cortical tubulointerstitial fibrosis (CTIFI: 4M, 0 versus 12M, 57.1 +/- 4.9; P < 0.01) was observed in the 12M rats. The severity of glomerulosclerosis and cortical tubulointerstitial fibrosis in the 12M group was augmented with OVX (GSI, 3.27 +/- 0.34; CTIFI, 74.4 +/- 9.2; P < 0.01 versus Intact at 12M) and attenuated with E(2) replacement ([GSI], 1.09 +/- 0.09; CTIFI, 49.2 +/- 6.8). In the 12M animals, OVX was also associated with increased deposition and expression of laminin (Intact, 228.1 +/- 6.7; OVX, 277.4 +/- 9.6 AU; P < 0.01), increased expression of TGF-beta (Intact, 85.0 +/- 23.0; OVX, 178.0 +/- 20.5 AU; P < 0.001), and decreased activity of cortical MMP-9 (Intact, 3.8 +/- 0.8; OVX, 2.4 +/- 0.6 AUC; P < 0.01). E(2) replacement opposed these effects (laminin, 229.9 +/- 6.2 AU; TGF-beta, 101.3 +/- 25.2 AU; MMP-9, 5.2 +/- 0.2 AUC). The severity of the disease in the 12M rats correlated with a modest decrease in creatinine clearance (Intact, 0.26 +/- 0.01; OVX, 0.22 +/- 0.01; OVX+E(2), 0.28 +/- 0.01 mg/min per 100 g) and increase in BUN (Intact, 20.3 +/- 2.1; OVX, 32.6 +/- 5.1; OVX+E(2), 24.3 +/- 2.4 mg/dl). The authors conclude that E(2) is renoprotective in the aging DSS rat by attenuating glomerulosclerosis and tubulointerstitial fibrosis.

My notes (saved in your browser only)

Citation neighborhood (sparse)

Too few in-corpus citations on either side for a chart; here are the lists.

Cites (1)

Cited by (1)

References (52)

Cited by (1)

Source provenance

openalex
last seen: 2026-06-10T17:14:06.276822+00:00
unpaywall
last seen: 2026-06-16T06:25:30.133384+00:00
License: CC0 · commercial use OK