Dataset Information

Renal interstitial fibroblasts coproduce erythropoietin and renin under anaemic conditions.

ABSTRACT:

Background

Erythrocyte mass contributes to maintaining systemic oxygen delivery and blood viscosity, with the latter being one of the determinants of blood pressure. However, the physiological response to blood pressure changes under anaemic conditions remain unknown.

Methods and findings

We show that anaemia decreases blood pressure in human patients and mouse models. Analyses of pathways related to blood pressure regulation demonstrate that anaemia enhances the expression of the gene encoding the vasopressor substance renin in kidneys. Although kidney juxtaglomerular cells are known to continuously produce renin, renal interstitial fibroblasts are identified in the present study as a novel site of renin induction under anaemic hypotensive conditions in mice and rats. Notably, some renal interstitial fibroblasts are found to simultaneously express renin and the erythroid growth factor erythropoietin in the anaemic mouse kidney. Antihypertensive agents but not hypoxic stimuli induced interstitial renin expression, suggesting that blood pressure reduction triggers interstitial renin induction in anaemic mice. The interstitial renin expression was also detected in injured fibrotic kidneys of the mouse and human, and the renin-expressing interstitial cells in murine fibrotic kidneys were identified as myofibroblasts originating from renal interstitial fibroblasts. Since the elevated expression levels of renin in fibrotic kidneys along with progression of renal fibrosis were well correlated to the systemic blood pressure increase, the renal interstitial renin production seemed to affect systemic blood pressure.

Interpretation

Renal interstitial fibroblasts function as central controllers of systemic oxygen delivery by producing both renin and erythropoietin.

Funding

Grants-in-Aid from Japan Society for the Promotion of Science (JSPS) KAKENHI (17K19680, 15H04691, and 26111002) and the Takeda Science Foundation.

SUBMITTER: Miyauchi K

PROVIDER: S-EPMC7841315 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Renal interstitial fibroblasts coproduce erythropoietin and renin under anaemic conditions.

Miyauchi Kenichiro K Nakai Taku T Saito Sakae S Yamamoto Tae T Sato Koji K Kato Koichiro K Nezu Masahiro M Miyazaki Mariko M Ito Sadayoshi S Yamamoto Masayuki M Suzuki Norio N

EBioMedicine 20210125

<h4>Background</h4>Erythrocyte mass contributes to maintaining systemic oxygen delivery and blood viscosity, with the latter being one of the determinants of blood pressure. However, the physiological response to blood pressure changes under anaemic conditions remain unknown.<h4>Methods and findings</h4>We show that anaemia decreases blood pressure in human patients and mouse models. Analyses of pathways related to blood pressure regulation demonstrate that anaemia enhances the expression of the ...[more]

PMID: 33508746

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Dataset Information

Renal interstitial fibroblasts coproduce erythropoietin and renin under anaemic conditions.

Background

Methods and findings

Interpretation

Funding

Publications

Renal interstitial fibroblasts coproduce erythropoietin and renin under anaemic conditions.

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