GDF11 improves tubular regeneration after acute kidney injury in elderly mice.

Ying Zhang,Guangyan Cai,Shaoyuan Cui,Dong Liu,Qi Huang,Xuefeng Sun,Qinggang Li,Xiangmei Chen

doi:10.1038/srep34624

Ying Zhang, Guangyan Cai + Show 6 more

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https://doi.org/10.1038/srep34624

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Abstract

The GDF11 expression pattern and its effect on organ regeneration after acute injury in the elderly population are highly controversial topics. In our study, GDF11/8 expression increased after kidney ischemia–reperfusion injury (IRI), and the relatively lower level of GDF11/8 in the kidneys of aged mice was associated with a loss of proliferative capacity and a decline in renal repair, compared to young mice. In vivo, GDF11 supplementation in aged mice increased vimentin and Pax2 expression in the kidneys as well as the percentage of 5-ethynyl-2′-deoxyuridine (EdU)-positive proximal tubular epithelial cells. GDF11 improved the renal repair, recovery of renal function, and survival of elderly mice at 72 h after IRI. Moreover, the addition of recombinant GDF11 to primary renal epithelial cells increased proliferation, migration, and dedifferentiation by upregulating the ERK1/2 pathway in vitro. Our study indicates that GDF11/8 in the kidney decreases with age and that GDF11 can increase tubular cell dedifferentiation and proliferation as well as improve tubular regeneration after acute kidney injury (AKI) in old mice.

Highlights

Metanephric mesenchyme and ureteric bud, and it is necessary in metanephric development[8,15]
Old mice had a larger increase in serum creatinine and BUN levels at 24 h after ischemia–reperfusion injury (IRI) than young mice that underwent the same length of ischemia (Supplementary Tables 1 and 2)
Noncomparable changes in serum BUN and creatinine levels were observed at 72 h after IRI, when young mice exhibited a steady decrease of BUN and creatinine levels but a lack of functional recovery was only observed in the old mice (Fig. 1a,b)

Summary

Introduction

Metanephric mesenchyme and ureteric bud, and it is necessary in metanephric development[8,15]. The GDF11 mRNA level is the highest in the kidney, and GDF11 expression in cancerous kidney tissue is much higher than that in normal kidney tissue[16]. These findings indicate that GDF11 is tightly associated with the proliferative state of the kidney. The in vivo effects of recombinant GDF (rGDF)[11] supplementation in aged mice on epithelial cell dedifferentiation and proliferation during the repair phase were assessed. The in vitro effects of the addition of rGDF11 to primary renal epithelial cells on proliferation, migration, and dedifferentiation as well as the ERK1/2 signaling pathway were determined

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