Funding:
This work was supported by the European Union’s Horizon 2020 research and innovation program by grant No 860329 (Marie-Curie ITN “STRATEGY-CKD”) and No 848011 (“DC-ren”).
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Legends to Figures
Figure 1: Study design. Urine samples from thirty-two T2DM patients were collected at two time points: pre-treatment and post-treatment with the intervention of GLP-1R agonists at 4.4 ± 4.11 months from first sample collection. Naturally occurring urinary peptides were quantified in the urine samples by CE-MS analysis, followed by statistical and bioinformatic analysis of the CE-MS generated urinary peptide profiles.
Figure 2 : Results of the urinary peptidomic analysis.(A) Distribution of peptide intensity for all the 329 sequenced urinary peptides identified in this study, red dots indicate the statistically significant peptides. (B) Volcano plot depicting the regulation of the 329 peptides in response to GLP-1R agonist treatment. (C) Urinary peptide profiles of the 70 significant peptides in pre-treatment, as obtained from CE-MS analysis. (D) Urinary peptide profiles of the 70 significant peptides in post-treatment, as obtained from CE-MS analysis. (E) Box and Whisker plots depicting the down-regulation of all the COL1A1 peptides, in response to GLP-1R agonists treatment. (F) Box and Whisker plots depicting the up- and down-regulation of all the COL3A1 peptides, in response to GLP-1R agonists treatment. (G) Alignment of identified peptide sequences in the primary structure of protein COL1A1. (H) Alignment of identified peptide sequences in this study in the primary structure of protein COL3A1. (I) Protein-protein interaction network including the 26 parental proteins giving the origin to 70 GLP-1R agonists-associated peptides. In, (G) and (H), the amino acids in green and red depict the down-regulated and up-regulated peptide sequences, respectively.
Figure 3: Hypothesis. The beneficial effects of GLP-1R agonists treatment on the different pathophysiological pathways associated with T2DM as suggested by the role of the down-regulated non-collagen peptides, respectively in each pathway.
Tables
Table 1: Clinical information of the T2DM patients in mean ± SD; from pre- and post-treatment with GLP-1R agonists