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.
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“…IGF2, a member of the insulin family, plays an important role in in brosis of lung, heart, liver and kidney [19,20] . In the study conducted by Bayati et al, induced pluripotent stem cells can inhibit experimental bleomycin-induced pulmonary brosis by regulating insulin-like growth factor signal [21] . In addition, IGF-2 and its receptors can activate the known TGF-β pro-brotic pathway and disrupt the balance of matrix proteases and their inhibitors, leading to excessive ECM deposition and inducing the differentiation of broblasts into myo broblasts, thus promoting the occurrence and development of brosis [20] .…”
Introduction
Acute exogenous lipoid pneumonia (AELP) is a rare disease. At present, the specific pathogenesis of AELP is unclear, and there is no safe and effective specific drug. The purpose of this study is to explore the biological processes, signal pathways and key proteins involved in AELP through proteomics, bioinformatics and polymerase chain reaction, so as to deepen the study of the pathogenesis of AELP.
Methods
The experimental rats were randomly divided into 2 groups: experiment group (inhaled 0.5 ml/kg of sewing machine oil) and control group (inhaled 0.5 ml/kg of normal saline). Collect the proteins in the upper lobe of the right lung of mice for proteomic sequencing to obtain the expression data, use the differential analysis software MaxQuant to screen the differentially expressed proteins (DEPs), and use the bioinformatics analysis method to carry out gene ontology function (GO), Kyoto Encyclopedia of genes and genomes (KEGG) analysis and protein-protein interaction (PPI) network construction for DEGs, Eleven key proteins (PADI4, IGF2, SMPDL3B, UHRF1, ANXA8, DEFB4, F3, MK167, SLC39A4, LIMD1 and GJA1) were detected by Reverse-transcription polymerase chain reaction (RT-PCR) for validation.
Results
A total of 1253 DEPs were obtained after comparing the data of the experimental group and the control group with the proteome, including 843 up-regulated proteins and 410 down-regulated proteins. Through the functional analysis of GO and KEGG, it is found that these DEPs mainly participate in the regulation process of integrin binding, proteoglycan binding, chemokine receptor binding, receiver regulator binding, and cytokine activity, and are significantly enriched in proteoglycan binding and other signal pathways. PPI network construction was carried out for DEPs to screen out proteins with high correlation, such as ACTN3, CX3CR1, CCR3, AGT, MYLPF. 11 proteins were verified by RT-PCR，compared with the control group, 9 proteins (PADI4, IGF2, SMPDL3B, UHRF1, ANXA8, MK167, SLC39A4, LIMD1 and GJA1) were significantly up-regulated in the experimental group.
Conclusion
Our findings identified that PADI4, IGF2, UHRF1, DEFB4 and GJA1 proteins may be potential diagnostic biomarker of AELP.
“…IGF2, a member of the insulin family, plays an important role in in brosis of lung, heart, liver and kidney [19,20] . In the study conducted by Bayati et al, induced pluripotent stem cells can inhibit experimental bleomycin-induced pulmonary brosis by regulating insulin-like growth factor signal [21] . In addition, IGF-2 and its receptors can activate the known TGF-β pro-brotic pathway and disrupt the balance of matrix proteases and their inhibitors, leading to excessive ECM deposition and inducing the differentiation of broblasts into myo broblasts, thus promoting the occurrence and development of brosis [20] .…”
Introduction
Acute exogenous lipoid pneumonia (AELP) is a rare disease. At present, the specific pathogenesis of AELP is unclear, and there is no safe and effective specific drug. The purpose of this study is to explore the biological processes, signal pathways and key proteins involved in AELP through proteomics, bioinformatics and polymerase chain reaction, so as to deepen the study of the pathogenesis of AELP.
Methods
The experimental rats were randomly divided into 2 groups: experiment group (inhaled 0.5 ml/kg of sewing machine oil) and control group (inhaled 0.5 ml/kg of normal saline). Collect the proteins in the upper lobe of the right lung of mice for proteomic sequencing to obtain the expression data, use the differential analysis software MaxQuant to screen the differentially expressed proteins (DEPs), and use the bioinformatics analysis method to carry out gene ontology function (GO), Kyoto Encyclopedia of genes and genomes (KEGG) analysis and protein-protein interaction (PPI) network construction for DEGs, Eleven key proteins (PADI4, IGF2, SMPDL3B, UHRF1, ANXA8, DEFB4, F3, MK167, SLC39A4, LIMD1 and GJA1) were detected by Reverse-transcription polymerase chain reaction (RT-PCR) for validation.
Results
A total of 1253 DEPs were obtained after comparing the data of the experimental group and the control group with the proteome, including 843 up-regulated proteins and 410 down-regulated proteins. Through the functional analysis of GO and KEGG, it is found that these DEPs mainly participate in the regulation process of integrin binding, proteoglycan binding, chemokine receptor binding, receiver regulator binding, and cytokine activity, and are significantly enriched in proteoglycan binding and other signal pathways. PPI network construction was carried out for DEPs to screen out proteins with high correlation, such as ACTN3, CX3CR1, CCR3, AGT, MYLPF. 11 proteins were verified by RT-PCR，compared with the control group, 9 proteins (PADI4, IGF2, SMPDL3B, UHRF1, ANXA8, MK167, SLC39A4, LIMD1 and GJA1) were significantly up-regulated in the experimental group.
Conclusion
Our findings identified that PADI4, IGF2, UHRF1, DEFB4 and GJA1 proteins may be potential diagnostic biomarker of AELP.
“…Herein, we used C57BL/6 mice as a multipurpose model for IPF research and chose the intratracheal route of Bleomycin administration as it produces a homogeneous distribution of fibrotic lesions among lung lobes. The rationale for using C57BL/6 mice is that they are susceptible to bleomycin-induced lung fibrosis, which is a widely used method to mimic IPF in animals [ 27 – 29 ]. Fig.…”
Background
The Wnt signaling pathway has been implicated in the pathogenesis of fibrotic disorders and malignancies. Hence, we aimed to assess the potential of the induced pluripotent stem cells (IPS) in modulating the expression of the cardinal genes of the Wnt pathway in a mouse model of idiopathic pulmonary fibrosis (IPF).
Methods
C57Bl/6 mice were randomly divided into three groups of Control, Bleomycin (BLM), and BLM + IPS; the BLM mice received intratracheal instillation of bleomycin, BLM + IPS mice received tail vein injection of IPS cells 48 h post instillation of the BLM; The Control group received Phosphate-buffered saline instead. After 3 weeks, the mice were sacrificed and Histologic assessments including hydroxy proline assay, Hematoxylin and Eosin, and Masson-trichrome staining were performed. The expression of the genes for Wnt, β-Catenin, Lef, Dkk1, and Bmp4 was assessed utilizing specific primers and SYBR green master mix.
Results
Histologic assessments revealed that the fibrotic lesions and inflammation were significantly alleviated in the BLM + IPS group. Besides, the gene expression analyses demonstrated the upregulation of Wnt, β-Catenin, and LEF along with the significant downregulation of the Bmp4 and DKK1 in response to bleomycin treatment; subsequently, it was found that the treatment of the IPF mice with IPS cells results in the downregulation of the Wnt, β-Catenin, and Lef, as well as upregulation of the Dkk1, but not the Bmp4 gene (P values < 0.05).
Conclusion
The current study highlights the therapeutic potential of the IPS cells on the IPF mouse model in terms of regulating the aberrant expression of the factors contributing to the Wnt signaling pathway.
“…To date, most endeavors in cell-based therapy for organspecific disorders have focused on two main areas; to make unlimited numbers of patient-specific tissue cells to regenerate the damaged organ, or to provide autologous genetically corrected cells for permanent corrective therapy of incurable and hereditary diseases of the liver [144], heart [145], kidney [146,147], and skin [148][149][150]. Furthermore, some studies utilized a limitless cell supply obtained from patient somatic cell-derived iPSCs for iPSC-based disease modeling, which is used to examine pathologic mechanisms and pharmacological interventions in various diseases such as organ fibrosis and failure [151][152][153][154][155]. The studies in all the above-mentioned scopes have been excluded from this review.…”
Section: Ipscs For the Treatment Of Fibrotic Diseasesmentioning
confidence: 99%
“…iPSCs also, can downregulate the pro-fibrotic growth factors IGF-1,2 [205], and repress several inflammatory mediators during pulmonary fibrosis, including TNF-α, IL-1β, IL-6, inducible nitric oxide synthase (iNOS) and nitric oxide (NO), but also PGE2. They also suppress the EMT process in lung tissues through upregulation of epithelial marker E-cadherin and downregulation of mesenchymal markers such as fibronectin, vimentin, and α-SMA.…”
Fibrosis is a pathological process, that could result in permanent scarring and impairment of the physiological function of the affected organ; this condition which is categorized under the term organ failure could affect various organs in different situations. The involvement of the major organs, such as the lungs, liver, kidney, heart, and skin, is associated with a high rate of morbidity and mortality across the world. Fibrotic disorders encompass a broad range of complications and could be traced to various illnesses and impairments; these could range from simple skin scars with beauty issues to severe rheumatologic or inflammatory disorders such as systemic sclerosis as well as idiopathic pulmonary fibrosis. Besides, the overactivation of immune responses during any inflammatory condition causing tissue damage could contribute to the pathogenic fibrotic events accompanying the healing response; for instance, the inflammation resulting from tissue engraftment could cause the formation of fibrotic scars in the grafted tissue, even in cases where the immune system deals with hard to clear infections, fibrotic scars could follow and cause severe adverse effects. A good example of such a complication is post-Covid19 lung fibrosis which could impair the life of the affected individuals with extensive lung involvement. However, effective therapies that halt or slow down the progression of fibrosis are missing in the current clinical settings. Considering the immunomodulatory and regenerative potential of distinct stem cell types, their application as an anti-fibrotic agent, capable of attenuating tissue fibrosis has been investigated by many researchers. Although the majority of the studies addressing the anti-fibrotic effects of stem cells indicated their potent capabilities, the underlying mechanisms, and pathways by which these cells could impact fibrotic processes remain poorly understood. Here, we first, review the properties of various stem cell types utilized so far as anti-fibrotic treatments and discuss the challenges and limitations associated with their applications in clinical settings; then, we will summarize the general and organ-specific mechanisms and pathways contributing to tissue fibrosis; finally, we will describe the mechanisms and pathways considered to be employed by distinct stem cell types for exerting anti-fibrotic events.
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