Induced Pluripotent Stem-cells Inhibit Experimental Bleomycin-induced Pulmonary Fibrosis Through Regulation of the Insulin-like  Growth Factor Signaling

Paria Bayati; Marjan Taherian; Mohammad-Ali Assarehzadegan; Mansoureh Soleimani; Hadi Poormoghim; Nazanin Mojtabavi

doi:10.18502/ijaai.v21i3.9800

Paria Bayati Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
Marjan Taherian Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
Mohammad-Ali Assarehzadegan Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
Mansoureh Soleimani Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
Hadi Poormoghim Scleroderma Study Group, Firuzgar Hospital, Iran University of Medical Sciences, Tehran, Iran
Nazanin Mojtabavi Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

DOI: https://doi.org/10.18502/ijaai.v21i3.9800

Keywords: Idiopathic pulmonary fibrosis; Induced pluripotent stem cells; Insulin-like growth factor Igf; IgfIrs1 protein

Abstract

Idiopathic pulmonary fibrosis (IPF) is among the illnesses with a high mortality rate, yet no specific cause has been identified; as a result, successful treatment has not been achieved. Among the novel approaches for treating such hard-to-cure diseases are induced pluripotent stem cells (IPSCs). Some studies have shown these cells’ potential in treating IPF. Therefore, we aimed to investigate the impact of IPSCs on insulin-like growth factor (Igf) signaling as a major contributor to IPF pathogenesis.

C57BL/6 mice were intratracheally instilled with Bleomycin (BLM) or phosphate-buffered saline; the next day, half of the bleomycin group received IPSCs through tail vein injection. Hydroxyproline assay and histologic examinations have been performed to assess lung fibrosis. The gene expression was evaluated using specific primers for Igf-1, Igf-2, and insulin receptor substrate 1 (Irs-1) genes and SYBR green qPCR master mix. The data have been analyzed using the 2^-ΔΔCT method.

The mice that received Bleomycin showed histological characteristics of the fibrotic lung injury, which was significantly ameliorated after treatment with IPSCs comparable to the control group. Furthermore, gene expression analyses revealed that in the BLM group, Igf1, Igf2, and Irs1 genes were significantly upregulated, which were returned to near-normal levels after treatment with IPSCs.

IPSCs could modulate the bleomycin-induced upregulation of Igf1, Igf2, and Irs1 genes. This finding reveals a new aspect of the therapeutic impact of the IPSCs on IPF, which could be translated into other fibrotic disorders.