Skip to main content
SpringerLink
Log in

The association of stem cell factor and soluble c-Kit (s-cKit) receptor serum concentrations with the severity and risk prediction of autism spectrum disorders

  • Original Article
  • Published:
Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

S tem cell factor (SCF) and its receptor (c-kit) signaling play important role in normal brain physiology including neurogenesis, synapse formation and spatial learning function of the hippocampal region of the brain. Autism spectrum disorder (ASD) is believed to result from abnormal development of neuronal networks and synaptic function. The aim of this study was to evaluate the SCF and its soluble receptor (s-ckit) serum concentrations in ASD. We also studied the serum SCF and s-ckit concentration with the severity of ASD (Levels 1-3; Mild, Moderate and severe, respectively). Ninety five patients with ASD (Mild; n=33, Moderate; n=32 and severe; n=30) and 82 normal controls age matched were included in this study. The serum concentration of SCF and s-ckit were measured by enzyme-linked immunosorbent assay (ELISA). The SCF serum concentration in control subjects was 3.45±1.06 ng/ml and in ASD was 3.41±0.92 ng/ml (P=0.88). The serum levels of s-ckit in control and ASD groups were 56.82±13.22 ng/ml and 67.11±12.00, respectively (P=001). We have also studied serum SCF and s-ckit concentrations with the severity of ASD. The serum concentration of SCF in mild, moderate and severe ASD groups was 3.45±0.93, 3.4±0.87 and 3.43±0.98 ng/ml, respectively (P>0.05) and for s-ckit was 48.77±9.28, 61.66±12.18 and 93.11±14.81ng/ml, respectively (P<0.05). The result of this study suggests that serum s-cKit concentrations may provide a reliable and practical indicator of ASD and positively correlated with disease severity. It is also concluded that s-cKit might be involved in the pathophysiology of ASD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

A submission to the journal of Metabolic Brain Disease implies that materials described in the manuscript, including all relevant raw data, will be freely available to any researcher wishing to use them for non-commercial purposes, without breaching participant confidentiality.

References

  • American Psychiatric Association (2013) Diagnostic and Statistical Manual of Mental Disorders: DSM-5, 5 edn. American Psychiatric Association, Washington, DC, p 947

    Book  Google Scholar 

  • Benvenuto A, Moavero R, Alessandrelli R et al (2009) Syndromic autism: causes and pathogenetic pathways. World J Pediatr 5:169–176

    Article  Google Scholar 

  • Bowen D, Yancik S, Bennett L et al (1993) Serum stem cell factor concentration in patients with myelodysplastic syndromes. Br J Haematol 85:63–66

    Article  CAS  Google Scholar 

  • Dahlen DD, Lin NL, Liu YC et al (2001) Soluble Kit receptor blocks stem cell factor bioactivity in vitro. Leuk Res 25:413–421

    Article  CAS  Google Scholar 

  • Elsabbagh M, Divan G, Koh YJ et al (2012) Global prevalence of autism and other pervasive developmental disorders. Autism Res 5:160–179

    Article  Google Scholar 

  • Erlandsson A, Larsson J, Forsberg-Nilsson K (2004) Stem cell factor is a chemoattractant and a survival factor for CNS stem cells. Exp Cell Res 301:201–210

    Article  CAS  Google Scholar 

  • Hirata T, Morii E, Morimoto M et al (1993) Stem cell factor induces outgrowth of c-kit-positive neurites and supports the survival of c-kit-positive neurons in dorsal root ganglia of mouse embryos. Development 119:49–56

    Article  CAS  Google Scholar 

  • Jin K, Mao XO et al (2002) Stem cell factor stimulates neurogenesis in vitro and in vivo. J Clin Invest 110:311–319

    Article  CAS  Google Scholar 

  • Kalmarzi RN, Foroutan A, Abdi M et al (2019) Serum level of stem cell factor and its soluble receptor in aspirin-exacerbated respiratory disease. Immunotherapy 11:1283–1291

    Article  CAS  Google Scholar 

  • Kasamatsu S, Hachiya A, Higuchi K et al (2008) Production of the soluble form of KIT, s-KIT, abolishes stem cell factor-induced melanogenesis in human melanocytes. J Invest Dermatol 128:1763–1772

    Article  CAS  Google Scholar 

  • Katafuchi T, Li AJ, Hirota S et al (2000) Impairment of spatial learning and hippocampal synaptic potentiation in c-kit mutant rats. Learn Mem 7:383–392

    Article  CAS  Google Scholar 

  • Keshet E, Lyman SD, Williams DE et al (1991) Embryonic RNA expression patterns of the c-kit receptor and its cognate ligand suggest multiple functional roles in mouse development. EMBO J 10:2425–2435

    Article  CAS  Google Scholar 

  • Khalili M, Mashayekhi F, Salehi Z (2020) Association of Hepatocyte Growth Factor (HGF) genetic variation (S3735520) and HGF serum concentration in autism spectrum disorders: a case-control study. Caspian J Neurol Sci 6:3–10

    Article  Google Scholar 

  • Kim D, Im JO, Won et al (2003) Upregulation of c-Kit receptor and stem cell factor in cerebellar inhibitory synapses in response to kainic acid. J Neurosci Res 1:72–78

    Article  Google Scholar 

  • Lee Y, Jung J, Cho et al (2013) Increased SCF/c-kit by hypoxia promotes autophagy of human placental chorionic plate-derived mesenchymal stem cells via regulating the phosphorylation of mTOR. J Cell Biochem 114:79–88

    Article  CAS  Google Scholar 

  • Lennartsson J, Rönnstrand L (2012) Stem cell factor receptor/c-Kit: from basic science to clinical implications. Physiol Rev 92:1619–1649

    Article  CAS  Google Scholar 

  • Łukaszewicz-Zając M, Mroczko B et al (2017) Stem cell factor in the serum of patients with esophageal cancer in relation to its histological types. Arch Med Sci 13:1357–1364

    Article  Google Scholar 

  • Makowska JS, Cieslak M, Kowalski ML (2009) Stem cell factor and its soluble receptor (c-kit) in serum of asthmatic patients- correlation with disease severity. BMC Pulm Med 9:27

    Article  Google Scholar 

  • Mashayekhi F, Gholizadeh L (2011) Administration of anti-c-kit antibody into the cerebrospinal fluid leads to increased cell death in the developing cerebral cortex. Saudi J Biol Sci 18:261–266

    Article  CAS  Google Scholar 

  • Merkwitz C, Lochhead P, Tsikolia N et al (2011) Expression of KIT in the ovary, and the role of somatic precursor cells. Prog Histochem Cytochem 46:131–184

    Article  Google Scholar 

  • Mostafa GA, Bjørklund G, Urbina MA et al (2016) The levels of blood mercury and inflammatory-related neuropeptides in the serum are correlated in children with autism spectrum disorder. Metab Brain Dis 31:593–599

    Article  CAS  Google Scholar 

  • Pop B, Niculae A, Pop TL, Răchișan AL (2017) Individuals with autism have higher 8-Iso-PGF2alpha levels than controls, but no correlation with quantitative assay of Paraoxonase 1 serum levels. Metab Brain Dis 32:1943–1950

    Article  CAS  Google Scholar 

  • Quan L, Zhao Y, Yi J, Shi XD, Zhong Y, Liu L (2021) Serum adiponectin levels are reduced in autism spectrum disorder and association with severity of symptoms. Metab Brain Dis 36:491–498

    Article  CAS  Google Scholar 

  • Russo AJ, Krigsman A, Jepson B et al (2009) Decreased serum Hepatocyte Growth Factor (HGF) in autistic children with severe gastrointestinal disease. Biomark Insights 4:181–190

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sacai H, Sakoori K, Konno K et al (2020) Autism spectrum disorder-like behavior caused by reduced excitatory synaptic transmission in pyramidal neurons of mouse prefrontal cortex. Nat Commun 11:5140

    Article  CAS  Google Scholar 

  • Sala C, Vicidomini C, Bigi I et al (2015) Shank synaptic scaffold proteins: keys to understanding the pathogenesis of autism and other synaptic disorders. J Neurochem 135:849–858

    Article  CAS  Google Scholar 

  • Salmassi A, Zorn S, Mettler L et al (2011) Circulating concentration of stem cell factor in serum of stimulated IVF patients. Reprod Biomed Online 22:140–147

    Article  CAS  Google Scholar 

  • Sun L, Lee J, Fine HA (2004) Neuronally expressed stem cell factor induces neural stem cell migration to areas of brain injury. J Clin Invest 113:1364–1374

    Article  CAS  Google Scholar 

  • Tajima F, Tsuchiya H, Nishikawa K et al (2010) Hepatocyte growth factor mobilizes and recruits hematopoietic progenitor cells into liver through a stem cell factor-mediated mechanism. Hepatol Res 40:711–719

    Article  CAS  Google Scholar 

  • Tayel SI, El-Hefnway SM, Abd E (2017) Association of stem cell factor gene expression with severity and atopic state in patients with bronchial asthma. Respir Res 18:21

    Article  Google Scholar 

  • Verpelli C, Sala C (2012) Molecular and synaptic defects in intellectual disability syndromes. Curr Opin Neurobiol 22:530–536

    Article  CAS  Google Scholar 

  • Vitali R, Cesi V, Nicotra MR et al (2003) c-Kit is preferentially expressed in MYCN-amplified neuroblastoma and its effect on cell proliferation is inhibited in vitro by STI-571. Int J Cancer 106:147–152

    Article  CAS  Google Scholar 

  • Zhang SC, Fedoroff S (1997) Cellular localization of stem cell factor and c-kit receptor in the mouse nervous system. J Neurosci Res 47:1–15

    Article  CAS  Google Scholar 

  • Zhao LR, Singhal S, Duan WM, Mehta J, Kessler JA (2007) Brain repair by hematopoietic growth factors in a rat model of stroke. Stroke 38:2584–2591

    Article  Google Scholar 

  • Zhong HL, Xu CL, Chen GS et al (2017) Plasma SCF/c-kit levels in patients with dipper and non-dipper hypertension. Chin Med Sci J 32:232–238

    Article  Google Scholar 

Download references

Acknowledgements

This study was supported by the University of Guilan, Rasht, Iran.

Author information

Authors and Affiliations

  1. Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran

    Farhad Mashayekhi, Somayeh Shabani, Soheila Talesh Sasani & Zivar Salehi

Authors
  1. Farhad Mashayekhi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Somayeh Shabani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Soheila Talesh Sasani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zivar Salehi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization: [Farhad Mashayekhi], Methodology: [Somayeh Shabani and Soheila Talesh Sasani], Formal analysis and investigation: [Farhad Mashayekhi and Zivar Salehi], Writing - original draft preparation: [Farhad Mashayekhi]; Funding acquisition: [Farhad Mashayekhi], Resources: [Farhad Mashayekhi and Zivar Salehi], Supervision: [Farhad Mashayekhi].

Corresponding author

Correspondence to Farhad Mashayekhi.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mashayekhi, F., Shabani, S., Sasani, S.T. et al. The association of stem cell factor and soluble c-Kit (s-cKit) receptor serum concentrations with the severity and risk prediction of autism spectrum disorders. Metab Brain Dis 37, 619–624 (2022). https://doi.org/10.1007/s11011-021-00883-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-021-00883-5

Keywords

Search

Navigation