{"title":"Platelet-Derived Growth Factor Promotes Glomerular Mesangial Cells Differentiation of Human Bone Marrow Hematopoietic Stem Cells - An In Vitro Study","authors":"Surekha Kattaru, Samundeshwari Echambadi Loganathan, Sireesha Kodavala, Chandra Sekhar Chodimella, Venkata Gurunadha Krishna Sarma Potukuchi","doi":"10.1002/jcb.70012","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>Glomerular filtration function and homeostasis are largely due to the cross-talk between podocytes, endothelial cells, and mesangial cells (MCs). Any disturbance in this association causes glomerular diseases (GD). Cell-based therapies are the best option in the treatment of GD. It is contemplated that hematopoietic stem cells (HSCs) are best suited to regenerate these cells; earlier, we have shown the differentiation of HSCs into podocytes. In this study, MCs formation was initiated with retinoic acid (RA), BMP-7, and Activin A, resulting in comma-shaped intermediate mesoderm (IM) cells prominently expressing Osr1. Followed by inducing with EGF, FGF, and BMP-7, which resulted in elongated metanephric mesenchyme (MM) cells conspicuously expressing Pax2, Wt1, Foxd1, and Eya1. Finally, MM cells were induced with platelet-derived growth factor to form polygonal-shaped MCs expressing α-smooth muscle actin, desmin, CD44, and PDGFRβ. The growing MCs showed positivity to periodic acid Schiff's, and ANAE staining with a prominent expression of the Itga8 elucidating phagocytic property of MCs. These MCs showed conspicuous expression of CD133, notch-2, and telomerase, determining the quiescence nature with a 31.2% proliferation rate revealed through Ki-67 staining. The functionality of MCs was assessed by growing MCs in 5.5 and 25 mM glucose concentrations, and noticeable expression of angiotensinogen, angiotensin-I and II, angiotensin-converting enzyme, collagen-4, fibronectin, and TGFβ1 was observed in 25 mM concentration, while lowered expression of these genes was observed in 5.5 mM concentration explaining the role of MCs in regulating the filtration pressure. All these findings demonstrate that HSCs can rejuvenate the insulted glomerulus.</p>\n </div>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":"126 3","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of cellular biochemistry","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jcb.70012","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Glomerular filtration function and homeostasis are largely due to the cross-talk between podocytes, endothelial cells, and mesangial cells (MCs). Any disturbance in this association causes glomerular diseases (GD). Cell-based therapies are the best option in the treatment of GD. It is contemplated that hematopoietic stem cells (HSCs) are best suited to regenerate these cells; earlier, we have shown the differentiation of HSCs into podocytes. In this study, MCs formation was initiated with retinoic acid (RA), BMP-7, and Activin A, resulting in comma-shaped intermediate mesoderm (IM) cells prominently expressing Osr1. Followed by inducing with EGF, FGF, and BMP-7, which resulted in elongated metanephric mesenchyme (MM) cells conspicuously expressing Pax2, Wt1, Foxd1, and Eya1. Finally, MM cells were induced with platelet-derived growth factor to form polygonal-shaped MCs expressing α-smooth muscle actin, desmin, CD44, and PDGFRβ. The growing MCs showed positivity to periodic acid Schiff's, and ANAE staining with a prominent expression of the Itga8 elucidating phagocytic property of MCs. These MCs showed conspicuous expression of CD133, notch-2, and telomerase, determining the quiescence nature with a 31.2% proliferation rate revealed through Ki-67 staining. The functionality of MCs was assessed by growing MCs in 5.5 and 25 mM glucose concentrations, and noticeable expression of angiotensinogen, angiotensin-I and II, angiotensin-converting enzyme, collagen-4, fibronectin, and TGFβ1 was observed in 25 mM concentration, while lowered expression of these genes was observed in 5.5 mM concentration explaining the role of MCs in regulating the filtration pressure. All these findings demonstrate that HSCs can rejuvenate the insulted glomerulus.
期刊介绍:
The Journal of Cellular Biochemistry publishes descriptions of original research in which complex cellular, pathogenic, clinical, or animal model systems are studied by biochemical, molecular, genetic, epigenetic or quantitative ultrastructural approaches. Submission of papers reporting genomic, proteomic, bioinformatics and systems biology approaches to identify and characterize parameters of biological control in a cellular context are encouraged. The areas covered include, but are not restricted to, conditions, agents, regulatory networks, or differentiation states that influence structure, cell cycle & growth control, structure-function relationships.