Transcriptomic analysis of diabetic kidney disease and neuropathy in mouse models of type 1 and type 2 diabetes

ABSTRACT Diabetic kidney disease (DKD) and diabetic peripheral neuropathy (DPN) are common complications of type 1 (T1D) and type 2 (T2D) diabetes. However, the mechanisms underlying pathogenesis of these complications are unclear. In this study, we optimized a streptozotocin-induced db/+ murine model of T1D and compared it to our established db/db T2D mouse model of the same C57BLKS/J background. Glomeruli and sciatic nerve transcriptomic data from T1D and T2D mice were analyzed by self-organizing map and differential gene expression analysis. Consistent with prior literature, pathways related to immune function and inflammation were dysregulated in both complications in T1D and T2D mice. Gene-level analysis identified a high degree of concordance in shared differentially expressed genes (DEGs) in both complications and across diabetes type when using mice from the same cohort and genetic background. As we have previously shown a low concordance of shared DEGs in DPN when using mice from different cohorts and genetic backgrounds, this suggests that genetic background may influence diabetic complications. Collectively, these findings support the role of inflammation and indicate that genetic background is important in complications of both T1D and T2D.

Click here to download Table S1 Table S2.Glom Cluster 1 Genes Click here to download Table S2 Table S3.Glom Cluster 2 Genes Click here to download Table S3 Table S4.Glom Cluster 3 Genes Click here to download Table S4 Table S5.Glom Cluster 1 GO Enrichment Clustered Click here to download Table S5

Fig. S7 .
Fig. S7.Correlation between DKD parameters and DEGs of interest from T1D mice.Plot of pair-wise Pearson correlation of DKD parameters and differentially expressed genes of interest from the Glom of db/+ Ctrl and db/+ STZ T1D mice (n = 4-6/group).Positive correlations are represented in red and negative correlations in blue.Darkness of color and large circle size indicate a strong correlation.Factors are sorted by clusters and factors with strong positive correlations grouped to the same cluster.Significance was set at p < 0.05.Insignificant correlations are blank.

Fig. S8 .
Fig. S8.Correlation between DKD parameters and DEGs of interest from T2D mice.Plot of pair-wise Pearson correlation of DKD parameters and differentially expressed genes of interest from the Glom of db/+ Ctrl and db/db T2D mice (n = 4-6/group).Positive correlations are represented in red and negative correlations in blue.Darkness of color and large circle size indicate a strong correlation.Factors are sorted by clusters and factors with strong positive correlations grouped to the same cluster.Significance was set at p < 0.05.Insignificant correlations are blank.

Fig. S9 .
Fig. S9.Correlation between DPN parameters and DEGs of interest from T1D mice.Plot of pair-wise Pearson correlation of DPN parameters and differentially expressed genes of interest from the SCN of db/+ Ctrl and db/+ STZ T1D mice (n = 5-6/group).Positive correlations are represented in red and negative correlations in blue.Darkness of color and large circle size indicate a strong correlation.Factors are sorted by clusters and factors with strong positive correlations grouped to the same cluster.Significance was set at p < 0.05.Insignificant correlations are blank.

Fig. S10 .
Fig. S10.Correlation between DPN parameters and DEGs of interest from T2D mice.Plot of pair-wise Pearson correlation of DPN parameters and differentially expressed genes of interest from the SCN of db/+ Ctrl and db/db T2D mice (n = 5-6/ group).Positive correlations are represented in red and negative correlations in blue.Darkness of color and large circle size indicate a strong correlation.Factors are sorted by clusters and factors with strong positive correlations grouped to the same cluster.Significance was set at p < 0.05.Insignificant correlations are blank.

Table S6 .
Glom Cluster 2 GO Enrichment ClusteredClick here to download TableS6

Table S9 .
Glom Cluster 3 GO Enrichment ClusteredClick here to download TableS9

Table S11 .
SCN 5x5 SOM gene Module AssignmentClick here to download TableS11

Table S19 .
SCN Cluster 4 GO Enrichment ClusteredClick here to download TableS19

Table S20 .
SCN Cluster 5 GO Enrichment ClusteredClick here to download TableS20

Table S21 .
SCN Cluster 2 GO Enrichment ClusteredClick here to download TableS21

Table S22 .
SCN Cluster 3 GO Enrichment ClusteredClick here to download TableS22

Table S23 .
SCN Cluster 6 GO Enrichment ClusteredClick here to download TableS23

Table S27 .
SCN cont vs SCN STZ DEGsClick here to download TableS27

Table S31 .
Glom STZ unique DEGsClick here to download TableS31

Table S33 .
Glom common tissue DEGsClick here to download TableS33

Table S34 .
SCN STZ unique DEGsClick here to download TableS34

Table S36 .
SCN common tissue DEGsClick here to download TableS36

Table S37 .
Glom common tissue DEG GOClick here to download TableS37

Table S38 .
Glom common tissue DEG KEGGClick here to download TableS38

Table S39 .
Glom STZ unique DEG GOClick here to download TableS39

Table S40 .
Glom dbdb unique DEG GOClick here to download TableS40

Table S42 .
SCN common tissue DEG GOClick here to download TableS42

Table S43 .
SCN STZ unique DEG GO Click here to download Table S43 Disease Models & Mechanisms: doi:10.1242/dmm.050080:Supplementary information Disease Models & Mechanisms • Supplementary information

Table S44 .
SCN dbdb unique DEG GOClick here to download TableS44

Table S45 .
SCN dbdb unique DEG KEGGClick here to download TableS45

Table S46 .
Shared DEGs between SCN and Glom in STZ vs ctlClick here to download TableS46

Table S47 .
Shared STZ DEG GOClick here to download TableS47

Table S48 .
Shared STZ DEG KEGGClick here to download TableS48

Table S49 .
Shared DEGs between SCN and Glom in dbdb vs ctlClick here to download TableS49

Table S50 .
Shared dbdb DEG GOClick here to download TableS50