The effects of IGF-1 and erythropoietin on apoptosis and telomerase activity in necrotizing enterocolitis model

Mete Akisu; Burak Durmaz; Ozge Altun Koroglu; Sema Unlubay; Mehmet Yalaz; Haluk Akin; Utku Ates; Meral Baka; Ferda Ozkinay; Ozgur Cogulu; Nilgun Kultursay

doi:10.1038/s41390-020-01195-7

The effects of IGF-1 and erythropoietin on apoptosis and telomerase activity in necrotizing enterocolitis model

Pediatr Res. 2021 Sep;90(3):559-564. doi: 10.1038/s41390-020-01195-7. Epub 2020 Oct 23.

Authors

Mete Akisu¹, Burak Durmaz², Ozge Altun Koroglu¹, Sema Unlubay³, Mehmet Yalaz¹, Haluk Akin⁴, Utku Ates⁵, Meral Baka⁵, Ferda Ozkinay^{4

3}, Ozgur Cogulu^{4

3}, Nilgun Kultursay¹

Affiliations

¹ Division of Neonatology, Department of Pediatrics, Faculty of Medicine, Ege University, Izmir, Turkey.
² Department of Medical Genetics, Faculty of Medicine, Ege University, Izmir, Turkey. burak.durmaz@ege.edu.tr.
³ Division of Genetics and Teratology, Department of Pediatrics, Faculty of Medicine, Ege University, Izmir, Turkey.
⁴ Department of Medical Genetics, Faculty of Medicine, Ege University, Izmir, Turkey.
⁵ Department of Histology and Embryology, Faculty of Medicine, Ege University, Izmir, Turkey.

PMID: 33096541
DOI: 10.1038/s41390-020-01195-7

Abstract

Background: Apoptosis that occurs after hypoxia/reoxygenation (H/R) has an important role in the pathogenesis of necrotizing enterocolitis (NEC). Telomerase activity, showing the regeneration capacity, may also be important in the recovery process. Therefore, we aimed to investigate the effects of insulin-like growth factor-1 (IGF-1) and erythropoietin (EPO) on apoptosis and telomerase activity in an H/R model.

Methods: Young mice were divided into four groups each containing ten Balb/c mice. Group 1 (H/R) were exposed to H/R; group 2 and group 3 were pretreated with IGF-1 and EPO, respectively, for 7 days before H/R. Group 4 served as control. Intestinal injury was evaluated by histological scoring and assessment of apoptosis was performed by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) test. Proapoptotic and antiapoptotic gene expressions and telomerase activity were analyzed by real-time PCR.

Results: IGF-1- and EPO-treated animals had decreased histological damage and apoptosis, confirmed by TUNEL test and caspase activity. Telomerase activity was increased in these animals in addition to increased expression of antiapoptotic genes. However, proapoptotic gene expressions were not statistically different.

Conclusions: The protective effects of IGF-1 and EPO in H/R damage may be through increased expression of antiapoptotic genes and increased telomerase activity, especially for IGF-1.

Impact: This is a comprehensive study measuring various variables, namely IGF-1, EPO, apoptosis, apoptotic and antiapoptotic genes, and telomerase activity in the NEC model. The intestinal protective effects of IGF-1 and EPO in H/R damage may occur through increased expression of antiapoptotic genes and increased telomerase activity. To the best of our knowledge, telomerase activity has not been investigated in the NEC model before. Regarding our results, novel strategies may be implemented for the early definitive diagnosis, robust preventive measures, and effective treatment modalities for NEC.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / physiology*
Disease Models, Animal
Enterocolitis, Necrotizing / prevention & control*
Erythropoietin / physiology*
Insulin-Like Growth Factor I / physiology*
Mice
Mice, Inbred BALB C
Telomerase / metabolism*

Substances

insulin-like growth factor-1, mouse
Erythropoietin
Insulin-Like Growth Factor I
Telomerase