Insulin-like growth factor-1 effects on kidney development in preterm piglets
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Insulin-like growth factor-1 effects on kidney development in preterm piglets. / Zhong, Jingren; Doughty, Richard; Thymann, Thomas; Sangild, Per Torp; Nguyen, Duc Ninh; Muk, Tik.
In: Pediatric Research, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Insulin-like growth factor-1 effects on kidney development in preterm piglets
AU - Zhong, Jingren
AU - Doughty, Richard
AU - Thymann, Thomas
AU - Sangild, Per Torp
AU - Nguyen, Duc Ninh
AU - Muk, Tik
N1 - Funding Information: The authors declare that this study received funding from Takeda, MA, USA (grant number: B11035M-TAK607; grant recipient: Per Torp Sangild). The funder was not involved in the study design, execution, collection, analysis, interpretation of data, the drafting of this article or the decision to submit it for publication. JZ was supported by China Scholarship Council. Open access funding provided by Copenhagen University. Publisher Copyright: © The Author(s) 2024.
PY - 2024
Y1 - 2024
N2 - Background: Preterm birth disrupts fetal kidney development, potentially leading to postnatal acute kidney injury. Preterm infants are deficient in insulin-like growth factor 1 (IGF-1), a growth factor that stimulates organ development. By utilizing a preterm pig model, this study investigated whether IGF-1 supplementation enhances preterm kidney maturation. Methods: Cesarean-delivered preterm pigs were treated systemically IGF-1 or vehicle control for 5, 9 or 19 days after birth. Blood, urine, and kidney tissue were collected for biochemical, histological and gene expression analyses. Age-matched term-born pigs were sacrificed at similar postnatal ages and served as the reference group. Results: Compared with term pigs, preterm pigs exhibited impaired kidney maturation, as indicated by analyses of renal morphology, histopathology, and inflammatory and injury markers. Supplementation with IGF-1 reduced signs of kidney immaturity, particularly in the first week of life, as indicated by improved morphology, upregulated expression of key developmental genes, reduced severity and incidence of microscopic lesions, and decreased levels of inflammatory and injury markers. No association was seen between the symptoms of necrotizing enterocolitis and kidney defects. Conclusion: Preterm birth in pigs impairs kidney maturation and exogenous IGF-1 treatment partially reverses this impairment. Early IGF-1 supplementation could support the development of preterm kidneys. Impact: Preterm birth may disrupt kidney development in newborns, potentially leading to morphological changes, injury, and inflammation. Preterm pigs have previously been used as models for preterm infants, but not for kidney development. IGF-1 supplementation promotes kidney maturation and alleviates renal impairments in the first week of life in preterm pigs. IGF-1 may hold potential as a supportive therapy for preterm infants sensitive to acute kidney injury.
AB - Background: Preterm birth disrupts fetal kidney development, potentially leading to postnatal acute kidney injury. Preterm infants are deficient in insulin-like growth factor 1 (IGF-1), a growth factor that stimulates organ development. By utilizing a preterm pig model, this study investigated whether IGF-1 supplementation enhances preterm kidney maturation. Methods: Cesarean-delivered preterm pigs were treated systemically IGF-1 or vehicle control for 5, 9 or 19 days after birth. Blood, urine, and kidney tissue were collected for biochemical, histological and gene expression analyses. Age-matched term-born pigs were sacrificed at similar postnatal ages and served as the reference group. Results: Compared with term pigs, preterm pigs exhibited impaired kidney maturation, as indicated by analyses of renal morphology, histopathology, and inflammatory and injury markers. Supplementation with IGF-1 reduced signs of kidney immaturity, particularly in the first week of life, as indicated by improved morphology, upregulated expression of key developmental genes, reduced severity and incidence of microscopic lesions, and decreased levels of inflammatory and injury markers. No association was seen between the symptoms of necrotizing enterocolitis and kidney defects. Conclusion: Preterm birth in pigs impairs kidney maturation and exogenous IGF-1 treatment partially reverses this impairment. Early IGF-1 supplementation could support the development of preterm kidneys. Impact: Preterm birth may disrupt kidney development in newborns, potentially leading to morphological changes, injury, and inflammation. Preterm pigs have previously been used as models for preterm infants, but not for kidney development. IGF-1 supplementation promotes kidney maturation and alleviates renal impairments in the first week of life in preterm pigs. IGF-1 may hold potential as a supportive therapy for preterm infants sensitive to acute kidney injury.
UR - http://www.scopus.com/inward/record.url?scp=85193732700&partnerID=8YFLogxK
U2 - 10.1038/s41390-024-03222-3
DO - 10.1038/s41390-024-03222-3
M3 - Journal article
C2 - 38762663
AN - SCOPUS:85193732700
JO - Pediatric Research
JF - Pediatric Research
SN - 0031-3998
ER -
ID: 398544874