Role of heme oxygenase-1 in postnatal differentiation of stem cells: a possible cross-talk with microRNAs.
CONCLUSIONS
Heme oxygenase-1 (HO-1) converts heme to biliverdin, carbon monoxide, and ferrous ions, but its cellular functions are far beyond heme metabolism. HO-1 via heme removal and degradation products acts as a cytoprotective, anti-inflammatory, immunomodulatory, and proangiogenic protein, regulating also a cell cycle. Additionally, HO-1 can translocate to nucleus and regulate transcription factors, so it can also act independently of enzymatic function.


BACKGROUND
Recently, a body of evidence has emerged indicating a role for HO-1 in postnatal differentiation of stem and progenitor cells. Maturation of satellite cells, skeletal myoblasts, adipocytes, and osteoclasts is inhibited by HO-1, whereas neurogenic differentiation and formation of cardiomyocytes perhaps can be enhanced. Moreover, HO-1 influences a lineage commitment in pluripotent stem cells and maturation of hematopoietic cells. It may play a role in development of osteoblasts, but descriptions of its exact effects are inconsistent.


RESULTS
In this review we discuss a role of HO-1 in cell differentiation, and possible HO-1-dependent signal transduction pathways. Among the potential mediators, we focused on microRNA (miRNA). These small, noncoding RNAs are critical for cell differentiation. Recently we have found that HO-1 not only influences expression of specific miRNAs but also regulates miRNA processing enzymes.


CONCLUSIONS
It seems that interplay between HO-1 and miRNAs may be important in regulating fates of stem and progenitor cells and needs further intensive studies.
1 Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University , Krakow, Poland .
Magdalena
M
Kozakowska
Krzysztof
K
Szade
Jozef
J
Dulak
Alicja
A
Jozkowicz
D000818:Animals; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000201:enzymology* / Q000502:physiology; D006410:Hematopoiesis; D051547:Heme Oxygenase-1; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D009369:Neoplasms / Q000201:enzymology / Q000473:pathology; D058953:Neural Stem Cells / Q000201:enzymology* / Q000502:physiology; D010006:Osteoblasts / Q000201:enzymology; D010010:Osteoclasts / Q000201:enzymology; D015398:Signal Transduction
D035683:MicroRNAs; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1