DKK1 Positively Correlates with Lung Function in COPD Patients and Reduces Airway Inflammation

Figures & data

Table 1 Characteristics of Healthy Controls, Stable COPD and AECOPD Patients

Characteristics	Healthy Controls (n=36)	Stable COPD Patients (n=25)	AECOPD Patients (n=10)	P-value
Age, years	48.44 ± 7.92	64.20 ± 8.09	71.50 ± 8.34	< 0.0001*
Sex, male/female	32/4	20/5	9/1	0.570
BMI, kg/m^2	22.13 ± 2.67	23.26 ± 3.29	22.01 ± 2.66	0.281
Smoking history, Never-smoker/smoker,	22/14	7/18	1/9	0.003*
FVC, L	3.49 ± 0.65	2.39 ± 0.74	2.05 ± 0.69	< 0.0001*
FEV1, L	3.14 ± 0.62	1.23 ± 0.52	1.03 ± 0.50	< 0.0001*
FEV1/FVC, %	90.36 ± 8.24	51.13 ± 12.12	48.56 ± 11.34	< 0.0001*
FEV1/Pre, %	103.75 ± 14.57	51.28 ± 19.14	47.90 ± 28.19	< 0.0001*
DKK1, pg/mL	5317.61 ± 1317.20	3866.72 ± 775.33	3482.10± 841.25	< 0.0001*

Note: *p<0.05, the result is statistically significant.

Figure 1 Levels of DKK1 in serum.

Notes: (A) The DKK1 levels in stable COPD (n=25) and AECOPD patients (n=10) were significantly lower than those in healthy subjects (n=36). (B) No statistical difference between smokers and nonsmokers in healthy subjects or in COPD patients. (C) GOLD stage III–IV patient serum showed greatest decrease in DKK1 compared to that of healthy subjects and GOLD stage I–II patients. DKK1, Dickkopf‐1; GOLD=Global Initiative for Chronic Obstructive Lung Disease. *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001.

Table 2 Correlation Between DKK1 and Lung Function

	Linear Correlation		Partial Correlation
	DKK1		DKK1
	r/rho	p	r	p
FVC	0.462	<0.0001*	0.229	0.063
FEV1	0.570	<0.0001*	0.358	0.003*
FEV1/FVC	0.590	<0.0001*	0.377	0.002*
FEV1/Pre	0.517	<0.0001*	0.346	0.004*

Note: *p<0.05, the result is statistically significant.

Figure 2 Correlation Between FVC, FEV1, FEV1/FVC, FEV1/Pre and DKK1.

Notes: DKK1 levels were found to be positively correlated with (A) FVC (r=0.462, p<0.0001), (B) FEV1 (r=0.570, p<0.0001), (C) FEV1/FVC (rho=0.590, p<0.0001), and (D) FEV1 (rho=0.517, p<0.0001). Pearson’s correlation coefficient (r) and Spearman’s rho were used to determine the correlation.

Table 3 Multiple Linear Regression Analysis

Parameter	R Square	Durbin-Watson	Unstandardized B	P-valve	VIF
Age	0.398	2.089	−17.807	0.293	2.485
BMI			95.256	0.038*	1.012
FVC			−250.336	0.475	6.034
FEV1			775.820	0.016*	7.550
Sex			435.982	0.354	1.586
Smoking history			179.747	0.593	1.635

Note: *p<0.05, the result is statistically significant.

Figure 3 DKK1 regulated LRP6 and airway inflammation, andrographolide elevated DKK1 and LRP6 and reduced airway inflammation.

Notes: (A) Detection of TNF-α, IL-6 and IL-8 in the cell supernatant after treatment of cells with different concentrations of CSE. (B) Western blot and PCR showed changes of DKK1 and LRP6 after CSE treatment. (C) Cells were pre-transfected with DKK1 overexpression plasmid or Andrographolide, followed by treatment with CSE, Western blot was used to detect protein levels. (D) Changes in TNF-α, IL-6 and IL-8 in cell supernatants in different treatment groups. Andro: Andrographolide. *p<0.05 with, **p<0.01, ****p<0.0001, respect to the blank group, ^#p< 0.05, ^####p<0.0001, with respect to the CD513B-1+2% CSE group, ^Δp < 0.05 with respect to the 2% CSE group.