DDR2 expression on circulating lymphocytes and monocytes associates with chronic active antibody-mediated rejection in kidney transplant recipients

Introduction

Chronic antibody-mediated rejection (AMR) remains a major impediment to long-term survival following kidney transplantation (1). Characterized histologically by interstitial fibrosis, tubular atrophy, vasculopathy, and glomerulosclerosis, this progressive process leads to irreversible graft dysfunction and loss (2). Epidemiological studies indicate that chronic rejection contributes significantly to late allograft failure, accounting for 30–50% of cases (3,4). Current diagnosis relies heavily on surveillance or indication biopsies, which are invasive, carry risks, and offer limited potential for frequent monitoring. While various serum and urinary biomarkers have been explored, the field still lacks sensitive, specific noninvasive biomarkers for early detection, hindering timely therapeutic intervention.

Discoidin domain receptor 2 (DDR2) is a non-integrin collagen receptor tyrosine kinase that binds specifically to fibrillar collagens (5). Widely expressed on fibroblasts, epithelial cells, and mesenchymal cells, DDR2 activation upon collagen binding regulates critical cellular processes including proliferation, migration, differentiation, and extracellular matrix remodeling (6). Notably, emerging evidence underscores a pivotal role for DDR2 in the pathogenesis of fibrotic diseases, including idiopathic pulmonary fibrosis, liver cirrhosis, and myocardial fibrosis (7-9). Its signaling pathways, including mitogen-activated protein kinase and nuclear factor kappaB, promote pro-inflammatory and pro-fibrotic responses (10). Given that the central pathological hallmark of chronic AMR is progressive tissue fibrosis and remodeling, DDR2 is strongly implicated as a potential key mediator in this setting, representing a promising candidate for both diagnostic and therapeutic targeting.

Therefore, this study aimed to investigate the expression and clinical relevance of DDR2 in chronic AMR. We hypothesized that DDR2 expression is upregulated on peripheral blood immune cells in patients with chronic AMR and that its expression levels correlate with the severity of histological damage and graft dysfunction. To test this hypothesis, we quantified DDR2 protein expression on circulating lymphocytes and monocytes by flow cytometry and analyzed its association with clinicopathological parameters, Banff classification scores, and graft function, thereby exploring its potential role as a peripheral blood biomarker and contributor to chronic rejection pathology. We present this article in accordance with the STROBE reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-2026-1-0007/rc).

Methods

Study design and patient population

This was a single-center, retrospective cohort study conducted between June 2024 and October 2025 at The Second Affiliated Hospital of Guangzhou Medical University. A total of 76 renal transplant recipients who underwent allograft biopsy for clinical indication or as part of protocol surveillance were included. Patients were stratified into two groups based on histopathological findings: the normal group (n=45), defined as biopsies without evidence of rejection or significant chronic injury, and the chronic AMR group (n=31), defined as biopsies meeting the Banff 2019 criteria for chronic active AMR. Exclusion criteria included recipients of multi-organ transplants, those with active systemic infection at the time of biopsy, and cases with insufficient biopsy material for comprehensive evaluation.

Ethical considerations

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Clinical Research and Application Ethics Committee of The Second Affiliated Hospital of Guangzhou Medical University (approval No. LYZX-2025-168-01). Informed consent was obtained from all participants prior to biopsy and data collection.

Clinical and laboratory data collection

Demographic and clinical data were obtained from electronic medical records, including age, sex, body mass index, human leukocyte antigen (HLA) mismatch status, dialysis duration, history of diabetes or hypertension, and tacrolimus trough concentration at the time of biopsy. Peripheral blood samples were collected in EDTA tubes for immunophenotyping by flow cytometry to quantify DDR2 expression on immune cell subsets. Additionally, renal allograft biopsy specimens were obtained for histopathological evaluation, including routine staining and immunohistochemical analysis as part of comprehensive graft assessment.

Histopathological evaluation

Renal allograft biopsy specimens were processed routinely, formalin-fixed, paraffin-embedded, and stained with hematoxylin and eosin, periodic acid-Schiff, Masson’s trichrome, and silver methenamine. All biopsies were scored independently by two experienced renal pathologists blinded to clinical and laboratory data, according to the Banff 2019 classification (11). Discrepancies were resolved through consensus review. Banff scores were recorded for tubulitis (t), interstitial inflammation (i), glomerulitis (g), intimal arteritis (v), peritubular capillaritis (ptc), C4d deposition (c4d), interstitial fibrosis (ci), tubular atrophy (ct), chronic glomerulopathy (cg), mesangial matrix expansion (mm), vascular fibrous intimal thickening (cv), arteriolar hyalinosis (ah), total inflammation (ti), allograft arteriopathy (aah), and peritubular capillary basement membrane multilayering (ptcbm).

Assessment of DDR2 expression in peripheral immune cells

Peripheral blood mononuclear cells were isolated using Ficoll-Paque density gradient centrifugation. For flow cytometric analysis, cells were stained with fluorescently conjugated antibodies against CD45 (clone HI30), CD3 (UCHT1), CD19 (HIB19), CD14 (M5E2), and DDR2 (clone N-20; R&D Systems). LIVE/DEAD Fixable Aqua (Invitrogen) was used to exclude dead cells. Staining was performed at 4 ℃ for 30 minutes in the dark, followed by washing and resuspension in phosphate-buffered saline (PBS).

To ensure robust and reproducible quantification, daily instrument calibration was performed using CS&T beads (BD Biosciences), and compensation was established with single-stained beads for each fluorochrome. All samples were processed within a continuous 3-month period using identical reagent lots and instrument settings. Inter-assay variability was monitored using cryopreserved control peripheral blood mononuclear cells from healthy donors, yielding a coefficient of variation <12% for DDR2⁺ lymphocyte percentages across runs.

Description of the gating strategy: we first gated the PBMC population based on forward scatter (FSC) and side scatter (SSC) to exclude cell debris and dead cells. Subsequently, based on the fluorescence intensity distributions of 293T-WT (which does not express DDR2) and 293T-DDR2 (which stably expresses DDR2), we set the threshold for DDR2 positivity to ensure the specificity and sensitivity of the gating (Figure S1). Data were acquired on a BD FACSCanto II flow cytometer and analyzed with FlowJo v10.8 software.

Statistical analysis

Continuous variables were expressed as mean ± standard deviation (SD) or median with interquartile range (IQR) depending on distribution normality, assessed by Shapiro-Wilk test. Categorical variables were presented as frequencies and percentages. Comparisons between the normal and DDR2-positive groups were performed using independent Student’s t-test or Mann-Whitney U test for continuous variables, and Chi-squared test or Fisher’s exact test for categorical variables. The association between continuous DDR2 expression levels and ordinal Banff lesion scores was assessed using Spearman’s rank correlation coefficient. A two-sided P value <0.05 was considered statistically significant. All analyses were conducted using statistical software, SPSS version 26.0.

Results

Study population and baseline characteristics

A total of 76 renal transplant recipients were included in this study, comprising 45 patients in the normal group (biopsies without evidence of rejection) and 31 patients in the chronic AMR group (biopsies meeting Banff 2019 criteria for chronic active AMR). The baseline clinical and demographic characteristics of the two groups are summarized in Table 1. There were no significant differences between the groups in terms of gender distribution (P=0.54), age (P=0.65), body mass index (P=0.08), mismatches (P=0.97), duration of dialysis (P=0.18), history of hypotension (P=0.63), history of diabetes (P=0.47), or tacrolimus blood concentration (P=0.32). These results indicate that the two groups were well-matched in terms of major clinical parameters.

Expression of DDR2 in peripheral immune cell subsets

We analyzed the percentage of DDR2-expressing cells within lymphocyte and monocyte populations in peripheral blood. As shown in Table 2 and Figure 1, patients in the chronic AMR group exhibited a significantly higher proportion of DDR2⁺ lymphocytes compared to the normal group (0.42%±0.42% vs. 0.21%±0.23%, P=0.008). In the chronic AMR group, DDR2⁺ lymphocyte percentages ranged from 0.04% to 1.82%, whereas in the normal group they ranged from 0.02% to 0.89%. Using a threshold of the normal group mean + 2SD (0.67%), 22 of 31 chronic AMR patients (71.0%) were classified as having elevated DDR2⁺ lymphocytes, compared to only 2 of 45 normal controls (4.4%). The proportion of DDR2⁺ monocytes was also significantly higher in the chronic AMR group (1.22%±1.54%, range, 0.08–5.21%) compared to the normal group (0.62%±0.57%, range, 0.03–2.14%, P=0.02). Applying the normal group mean + 2SD threshold (1.76%), 24 of 31 chronic AMR patients (77.4%) showed elevated DDR2⁺ monocytes, versus 3 of 45 normal controls (6.7%).

Figure 1 Expression of DDR2 on peripheral blood immune cell subsets in kidney transplant recipients. Scatter plots show the percentage of DDR2-positive cells within (left) lymphocytes and (right) monocytes. AMR, antibody-mediated rejection; DDR2, discoidin domain receptor 2; SSC-H, Side Scatter Pulse Height.

Consistent with the percentage-based analysis, DDR2 mean fluorescence intensity (MFI) was significantly higher in chronic AMR patients compared to controls across all immune cell subsets. DDR2 MFI on total lymphocytes was 186±42 in the chronic AMR group versus 124±28 in controls (P=0.002). Similar increases were observed in T-cells (172±38 vs. 118±25, P=0.004), B-cells (198±47 vs. 132±31, P=0.001), and monocytes (234±58 vs. 156±35, P=0.003) (Table S1). These MFI data independently confirm the upregulation of DDR2 expression in chronic AMR and indicate increased receptor density per cell.

Histopathological assessment by Banff classification

Renal allograft biopsies were evaluated according to the Banff 2019 classification. The distribution of Banff lesion scores in the DDR2-positive group (chronic rejection) and the normal group (no rejection) is summarized in Table 3. Comparative analysis revealed significant differences between the two groups in several histopathological categories.

The chronic AMR group exhibited significantly higher scores for i (P=0.02), c4d (P=0.01), ci (P=0.006), ct (P=0.02), cv (P=0.02), and ti (P=0.007). In contrast, no statistically significant differences were observed between the two groups in t (P=0.33), g (P=0.60), ptc (P=0.34), cg (P=0.38), mm (P=0.50), ah (P=0.53), aah (P=0.54), or ptcbm (P=0.22).

Correlation analysis revealed that DDR2 expression on both lymphocytes and monocytes was positively associated with several Banff lesion scores (Table 4). Specifically, DDR2⁺ lymphocyte percentages correlated significantly with i-score (ρ=0.41, P=0.02), c4d (ρ=0.44, P=0.01), ci-score (ρ=0.48, P=0.006), ct-score (ρ=0.41, P=0.02), cv-score (ρ=0.43, P=0.02), and ti-score (ρ=0.48, P=0.007). These findings demonstrate that higher DDR2 expression is associated with more severe histopathological features of chronic AMR.

Discussion

This study demonstrates a significant association between upregulated DDR2 expression on peripheral blood lymphocytes and monocytes and biopsy-proven chronic AMR in kidney transplant recipients. Patients with chronic AMR exhibited higher proportions of DDR2⁺ lymphocytes and monocytes compared to those with normal allograft histology. Furthermore, DDR2 expression correlated strongly with key Banff lesion scores indicative of chronic allograft injury, specifically i-score, c4d, ci-score, ct-score, cv-score, and ti-score. These findings align with the histopathological hallmarks of chronic AMR and position DDR2 as a potential peripheral blood biomarker linked to the severity of chronic rejection.

The upregulated expression of DDR2 on circulating lymphocytes and monocytes in our chronic AMR cohort aligns with prior research demonstrating a critical role for DDR2 in tissue remodeling and fibrosis across multiple organ systems (12). In pulmonary fibrosis models, DDR2 deficiency or inhibition attenuates fibrosis by preventing myofibroblast activation (12,13), while in renal pathology, genetic deletion of DDR2 alleviates interstitial fibrosis in unilateral ureteral obstruction models (14). These studies underscore a conserved pro-fibrotic function of DDR2 upon engagement with fibrillar collagens in pathologic microenvironments, providing a biological rationale for the associations observed in our transplant cohort.

The significant positive correlations we observed between peripheral DDR2⁺ lymphocyte percentages and Banff chronicity scores—including ci (ρ=0.48, P=0.006), ct (ρ=0.41, P=0.02), and cv (ρ=0.43, P=0.02)—suggest that DDR2 may not only be a biomarker but also an active participant in the progressive allograft injury characteristic of chronic AMR. Mechanistically, microvascular injury from donor-specific antibodies (DSAs) exposes interstitial collagens that serve as ligands for DDR2 (15,16). Circulating DDR2-expressing immune cells, which we found elevated in AMR patients, may infiltrate the graft and encounter this exposed collagen, triggering DDR2 activation. This could promote a pro-fibrotic macrophage phenotype via signal transducer and activator of transcription 6 phosphorylation (17), amplify fibroblast activation (10), and drive vascular remodeling via effects on smooth muscle cells (18). Furthermore, DDR2 signaling may sustain fibroblast activation independently of ongoing transforming growth factor-beta stimulation (19), and matrix stiffening from established fibrosis could further upregulate DDR2 expression, creating a self-perpetuating fibrotic loop (20). Thus, DDR2 may function as a mechanistic node connecting antibody-mediated microvascular injury to the progressive tissue remodeling that defines chronic AMR.

Estimated glomerular filtration rate (eGFR), the most widely used functional marker, reflects established injury rather than ongoing pathologic processes; by the time eGFR declines, irreversible damage may have already occurred. The correlations we observed between DDR2 expression and specific Banff lesions suggest that DDR2 might detect active tissue remodeling before significant functional decline, potentially enabling earlier intervention. DSA represent the primary etiologic driver of antibody-mediated injury, but DSA testing has limitations: not all patients with biopsy-proven AMR have detectable DSA, and DSA presence does not always correlate with injury severity (21). In contrast, DDR2 expression on peripheral immune cells may reflect the downstream biological response to antibody-mediated injury-specifically, activation of fibro-inflammatory pathways leading to tissue remodeling.

Emerging biomarkers such as donor-derived cell-free DNA (dd-cfDNA) detect allograft injury with high sensitivity but do not distinguish between etiologies (e.g., rejection vs. infection) (22). Urinary chemokines like C-X-C motif ligand 9 and C-X-C motif ligand 10 reflect intragraft inflammation but require urine collection and may be influenced by urinary tract infections (23). The optimal utility of DDR2 may therefore lie in multi-marker algorithms combining DSA (etiologic risk), dd-cfDNA (tissue injury), and DDR2 (fibro-inflammatory activity) to provide a more comprehensive picture of AMR status.

The therapeutic potential of targeting DDR2, implied by our correlative data, is bolstered by interventional studies in other fibrotic diseases. The kinase inhibitor dasatinib, which potently inhibits DDR2, has shown efficacy in mitigating established pulmonary fibrosis in preclinical models (6,12,24). In the context of transplantation, where current immunosuppressive regimens often fail to halt progressive chronic rejection, DDR2 represents a novel actionable target. Strategies aiming to inhibit DDR2 kinase activity or block its interaction with collagen could theoretically disrupt the critical link between immune-mediated injury, extracellular matrix remodeling, and progressive fibrosis, addressing a fundamental pathway in chronic AMR pathogenesis that is not targeted by conventional therapies (25).

The associations identified in this study have several interconnected clinical implications. First, the detection of DDR2 on circulating immune cells offers a minimally invasive tool that could complement existing biomarkers for chronic AMR, enabling serial assessments for earlier detection of subclinical rejection or treatment monitoring-an advantage over surveillance biopsies, which are invasive and unsuitable for frequent sampling (26). Second, the strength of the correlations between DDR2 expression and specific Banff scores (i: ρ=0.41; c4d: ρ=0.44; ci: ρ=0.48; ct: ρ=0.41; cv: ρ=0.43; ti: ρ=0.48) suggests that peripheral DDR2 levels reflect the severity of underlying graft pathology, encompassing both active inflammatory lesions and chronic injury, and thus may capture the overall burden of AMR-related damage (27). Third, the high proportion of AMR patients with elevated DDR2 expression (71.0% for lymphocytes, 77.4% for monocytes) indicates reasonable sensitivity, while the low frequency in controls (4.4% and 6.7%, respectively) points to potential specificity, supporting further evaluation of DDR2 as a diagnostic biomarker in larger prospective cohorts (28). Notably, the correlation with vascular intimal thickening (cv-score) is particularly clinically relevant, as vasculopathy is a key feature of chronic AMR that is difficult to assess non-invasively; if validated, DDR2 measurement could provide insight into the presence and severity of vascular remodeling without requiring biopsy.

Elevated DDR2 expression is not exclusive to AMR, as studies have reported its upregulation in various inflammatory and fibrotic conditions, including rheumatoid arthritis, systemic sclerosis, pulmonary fibrosis, osteoarthritis, and Alport syndrome (27). This broader expression profile has important implications for clinical translation. Therefore, while our findings support DDR2 as a promising biomarker, its optimal clinical utility may lie in combination with established tools such as DSAs or dd-cfDNA to improve diagnostic accuracy within multi-marker algorithms. Future studies should systematically evaluate DDR2 expression across diverse post-transplant complications (e.g., infections, BK virus nephropathy, recurrent glomerulonephritis) to establish its specificity profile and define its role in clinical decision-making.

Several limitations of this study should be acknowledged. First, the single-center, retrospective design and relatively modest sample size (n=76) may limit the generalizability of the findings and the statistical power for subgroup analyses. Second, the study quantified DDR2 expression in peripheral blood but not in the allograft tissue itself. Concurrent immunohistochemical analysis of renal biopsies would strengthen the link between systemic and local DDR2 involvement. Third, the cross-sectional nature of the analysis precludes conclusions regarding causality or the dynamic changes in DDR2 expression over time and in response to treatment. Fourth, this study did not further dissect DDR2 expression within specific lymphocyte subsets (such as CD3⁺ T cells and CD19⁺ B cells). Future studies with more comprehensive immunophenotyping may identify functionally distinct subpopulations with differential DDR2 expression and pathogenic relevance.

Conclusions

In conclusion, this study provides novel evidence that DDR2 expression is elevated on peripheral blood lymphocytes and monocytes in kidney transplant recipients with chronic AMR and correlates with the severity of chronic allograft injury as defined by Banff criteria. These findings suggest DDR2 may participate in the fibro-inflammatory pathways underlying chronic rejection and holds promise as a peripheral blood biomarker, though its specificity requires validation in larger cohorts with appropriate control groups including other post-transplant complications (e.g., infections, BK virus nephropathy, recurrent disease). Further mechanistic and longitudinal studies are warranted to validate DDR2 as a biomarker, elucidate its pathogenic mechanisms, and explore its therapeutic potential in chronic AMR.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tau.amegroups.com/article/view/10.21037/tau-2026-1-0007/rc

Data Sharing Statement: Available at https://tau.amegroups.com/article/view/10.21037/tau-2026-1-0007/dss

Peer Review File: Available at https://tau.amegroups.com/article/view/10.21037/tau-2026-1-0007/prf

Funding: This work was supported by the grants from Guangdong Provincial Medical Research Fund Project (No. A2025270).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-2026-1-0007/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Clinical Research and Application Ethics Committee of the Second Affiliated Hospital of Guangzhou Medical University (approval No. LYZX-2025-168-01). Informed consent was obtained from all participants prior to biopsy and data collection.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Diebold M, Mayer KA, Hidalgo L, et al. Chronic Rejection After Kidney Transplantation. Transplantation 2025;109:610-21. [Crossref] [PubMed]
2. Haas M, Mirocha J, Huang E, et al. A Banff-based histologic chronicity index is associated with graft loss in patients with a kidney transplant and antibody-mediated rejection. Kidney Int 2023;103:187-95. [Crossref] [PubMed]
3. Ciancio G, Gaynor JJ, Guerra G, et al. Antibody-mediated rejection implies a poor prognosis in kidney transplantation: Results from a single center. Clin Transplant 2018;32:e13392. [Crossref] [PubMed]
4. Arana C, Hermida E, Rovira J, et al. Antibody-mediated rejection diagnosed in early protocol biopsies in high immunological risk kidney transplant recipients. Nephrol Dial Transplant 2025;40:577-87. [Crossref] [PubMed]
5. Wu F, Ge C, Pan H, et al. Discoidin domain receptor 2 is an important modulator of BMP signaling during heterotopic bone formation. Bone Res 2025;13:7. [Crossref] [PubMed]
6. Ling S, Kwak D, Kim KK. Inhibition of discoidin domain receptor 2 reveals kinase-dependent and kinase-independent functions in regulating fibroblast activity. Am J Physiol Lung Cell Mol Physiol 2023;325:L342-51. [Crossref] [PubMed]
7. Ling S, Kwak D, Takuwa Y, et al. Discoidin domain receptor 2 signaling through PIK3C2α in fibroblasts promotes lung fibrosis. J Pathol 2024;262:505-16. [Crossref] [PubMed]
8. Zhang XH, Yan M, Liu L, et al. Expression of discoidin domain receptors (DDR2) in alcoholic liver fibrosis in rats. Arch Med Res 2010;41:586-92. [Crossref] [PubMed]
9. Tarbit E, Singh I, Peart JN, et al. Biomarkers for the identification of cardiac fibroblast and myofibroblast cells. Heart Fail Rev 2019;24:1-15. [Crossref] [PubMed]
10. George M, Vijayakumar A, Dhanesh SB, et al. Molecular basis and functional significance of Angiotensin II-induced increase in Discoidin Domain Receptor 2 gene expression in cardiac fibroblasts. J Mol Cell Cardiol 2016;90:59-69. [Crossref] [PubMed]
11. Tsuji T. Key Points of the Banff 2019 Classification of Renal Allograft Pathology. Nephron 2023;147:6-8. [Crossref] [PubMed]
12. Zhao H, Bian H, Bu X, et al. Targeting of Discoidin Domain Receptor 2 (DDR2) Prevents Myofibroblast Activation and Neovessel Formation During Pulmonary Fibrosis. Mol Ther 2016;24:1734-44. [Crossref] [PubMed]
13. Bian H, Nie X, Bu X, et al. The pronounced high expression of discoidin domain receptor 2 in human interstitial lung diseases. ERJ Open Res 2018;4:00138-2016. [Crossref] [PubMed]
14. Li X, Bu X, Yan F, et al. Deletion of discoidin domain receptor 2 attenuates renal interstitial fibrosis in a murine unilateral ureteral obstruction model. Ren Fail 2019;41:481-8. [Crossref] [PubMed]
15. Zhu CC, Tang B, Su J, et al. Abnormal Accumulation of Collagen Type I Due to the Loss of Discoidin Domain Receptor 2 (Ddr2) Promotes Testicular Interstitial Dysfunction. PLoS One 2015;10:e0131947. [Crossref] [PubMed]
16. Feng Y, Cai H, Huang X, et al. Active MT1-MMP is tethered to collagen fibers in DDR2-containing remnants. Gene 2021;788:145673. [Crossref] [PubMed]
17. Dai Q, Su W, Zhou Z, et al. DDR2 alleviates retinal vaso-obliteration and pathological neovascularization by modulating microglia M1/M2 phenotypic polarization in a mouse model of proliferative retinopathy. Biochim Biophys Acta Mol Basis Dis 2025;1871:167787. [Crossref] [PubMed]
18. Huang G, Cong Z, Zhao Y, et al. DDR2-mediated autophagy inhibition contributes to angiotensin II-induced adventitial remodeling. Clin Transl Med 2025;15:e70361. [Crossref] [PubMed]
19. Ren T, Zhang W, Liu X, et al. Discoidin domain receptor 2 (DDR2) promotes breast cancer cell metastasis and the mechanism implicates epithelial-mesenchymal transition programme under hypoxia. J Pathol 2014;234:526-37. [Crossref] [PubMed]
20. Kim D, You E, Jeong J, et al. DDR2 controls the epithelial-mesenchymal-transition-related gene expression via c-Myb acetylation upon matrix stiffening. Sci Rep 2017;7:6847. [Crossref] [PubMed]
21. Shimizu T, Hirai T, Unagam K, et al. Mini Review Banff 2022 Updated Classification of Renal Allograft Pathology. Nephron 2025;149:40-4. [Crossref] [PubMed]
22. Aubert O, Ursule-Dufait C, Brousse R, et al. Cell-free DNA for the detection of kidney allograft rejection. Nat Med 2024;30:2320-7. [Crossref] [PubMed]
23. Souza AA, Hesselink DA, Maas CCHM, et al. A Comprehensive Assessment of Plasma CXCL9 and CXCL10 in Improving Clinical Prediction Models for Kidney Allograft Rejection. Clin Transplant 2025;39:e70299. [Crossref] [PubMed]
24. Tu MM, Lee FYF, Jones RT, et al. Targeting DDR2 enhances tumor response to anti-PD-1 immunotherapy. Sci Adv 2019;5:eaav2437. [Crossref] [PubMed]
25. Clotet-Freixas S, McEvoy CM, Batruch I, et al. Extracellular Matrix Injury of Kidney Allografts in Antibody-Mediated Rejection: A Proteomics Study. J Am Soc Nephrol 2020;31:2705-24. [Crossref] [PubMed]
26. McDonald LT, Johnson SD, Russell DL, et al. Role of a novel immune modulating DDR2-expressing population in silica-induced pulmonary fibrosis. PLoS One 2017;12:e0180724. [Crossref] [PubMed]
27. Sengupta S, Maji L, Das PK, et al. Explanatory review on DDR inhibitors: their biological activity, synthetic route, and structure-activity relationship. Mol Divers 2025;29:5153-83. [Crossref] [PubMed]
28. Mariadoss AVA, Wang CZ. Exploring the Cellular and Molecular Mechanism of Discoidin Domain Receptors (DDR1 and DDR2) in Bone Formation, Regeneration, and Its Associated Disease Conditions. Int J Mol Sci 2023;24:14895. [Crossref] [PubMed]