Effects of Pemphigus Vulgaris Serum on the Expression of ATP2C1 and PKP3 in HaCaT Cells

Abstract Objective: To investigate the effects of serum from patients with pemphigus vulgaris (PV) on the transcription and protein expression level of calcium-transporting ATPase type 2C member 1 (ATP2C1) and plakophilin 3 (PKP3) in HaCaT cells. Methods: The HaCaT cells were divided into four groups: PV sera group, anti-Dsg3 monoclonal antibody group (AK23, positive control group), normal healthy serum group, and blank cell group. The groups were treated with corresponding different conditions for 24 hours. Quantitative polymerase chain reaction and Western blot were used to detect mRNA and protein levels of ATP2C1 and PKP3. Results: Compared with the blank group, the mRNA level of the ATP2C1 and PKP3 genes in PV sera group was significantly increased by 384% and 404%, respectively (both P < 0.001). The treatment of PV sera and anti-Dsg3 antibody increased PKP3 protein expression (P = 0.03 and P = 0.004) but decreased protein expression of ATP2C1 in HaCaT cells (both P < 0.001). Conclusions: Our study indicates that serum from patients with PV promotes both ATP2C1 and PKP3 transcription in HaCaT cells, implying that the two genes may be involved in the pathological process of PV.

[1]  J. Waschke,et al.  Plakophilin 1 but not plakophilin 3 regulates desmoglein clustering , 2019, Cellular and Molecular Life Sciences.

[2]  K. Amber,et al.  Synergy among non-desmoglein antibodies contributes to the immunopathology of desmoglein antibody–negative pemphigus vulgaris , 2019, The Journal of Biological Chemistry.

[3]  Junqin Liang,et al.  Naringenin protects keratinocytes from oxidative stress injury via inhibition of the NOD2-mediated NF-κB pathway in pemphigus vulgaris. , 2017, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[4]  Heng Xiao,et al.  The role of the ATP2C1 gene in Hailey–Hailey disease , 2017, Cellular and Molecular Life Sciences.

[5]  I. Screpanti,et al.  The loss of ATP2C1 impairs the DNA damage response and induces altered skin homeostasis: Consequences for epidermal biology in Hailey-Hailey disease , 2016, Scientific Reports.

[6]  L. Godsel,et al.  Plakophilin 3 mediates Rap1-dependent desmosome assembly and adherens junction maturation , 2014, Molecular biology of the cell.

[7]  Yumay Chen,et al.  Mechanisms of Mitochondrial Damage in Keratinocytes by Pemphigus Vulgaris Antibodies* , 2013, The Journal of Biological Chemistry.

[8]  M. Camilleri,et al.  Pemphigus Vulgaris Autoantibody Profiling by Proteomic Technique , 2013, PloS one.

[9]  R. Eming,et al.  IgG autoantibodies against desmocollin 3 in pemphigus sera induce loss of keratinocyte adhesion. , 2011, The American journal of pathology.

[10]  Guzin G Demirag,et al.  Expression of Plakophilins (PKP1, PKP2, and PKP3) in Gastric Cancers , 2011, Diagnostic pathology.

[11]  F. V. Roy,et al.  Serum plakophilin‐3 autoreactivity in paraneoplastic pemphigus , 2010, The British journal of dermatology.

[12]  R. Eming,et al.  Desmocollin 3-mediated Binding Is Crucial for Keratinocyte Cohesion and Is Impaired in Pemphigus* , 2009, The Journal of Biological Chemistry.

[13]  N. Cirillo,et al.  Cleavage of desmoglein 3 can explain its depletion from keratinocytes in pemphigus vulgaris , 2008, Experimental dermatology.

[14]  L. Lamant,et al.  [Antidesmoglein antibodies in a patient with Hailey-Hailey disease]. , 2012, Annales de dermatologie et de venereologie.

[15]  Y. Sullu,et al.  Expression of Plakophilins ( PKP 1 , PKP 2 , and PKP 3 ) in Gastric Cancers , 2011 .

[16]  K. Arnvig,et al.  Maturation , 1999, International Journal of Obesity.