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Kidney Week

Abstract: PO0653

Renal Type 1 Pericytes in the Development of Diabetic Kidney Disease

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Honda, Tâmisa Seeko, Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Foresto-Neto, Orestes, Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • da Silva, Ana Ruth Paolinetti Alves, Universidade Federal de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Santana, Fernanda P. R., Universidade Federal de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Ranfley, Hedden, Universidade Federal de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Watanabe, Ingrid Kazue Mizuno, Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Silva, Magaiver Andrade, Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Cenedeze, Marcos A., Universidade Federal de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Pacheco-Silva, Alvaro, Universidade Federal de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Birbrair, Alexander, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
  • Camara, Niels Olsen Saraiva, Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil

Group or Team Name

  • Transplantation Immunobiology Lab
Background

Pericytes are described as regulators and keepers of the vascular system. They can recognize and respond to inflammatory stimulus, through secretory and phenotype alterations. So far, the involvement of pericytes during diabetic kidney disease (DKD) has not been demonstrated yet, as well as how they can change its inflammatory and metabolic profile in this condition. In addition, not much is known about how these cells trigger DKD-associated injury and inflammation.

Methods

DKD was induced in NG2-Dsred mice by the combination of unilateral nephrectomy (UNx) and multiple low doses of streptozotocin (50 mg/Kg). UNx controls received only vehicle. All the mice were followed for 12 weeks. Urine glucose, protein/creatinine and albuminuria were evaluated as markers of renal function. NPHS1, KIM-1, IL-6, PKM2, HK2, CPT1a and LDH (qPCR), pericyte frequency/phenotype/secretion profiles (FACS) were assessed in kidney samples.

Results

DKD mice had an increased in protein/creatine ratio, as well as in glucosuria when compared to non-DKD mice (p<0.01). The impaired renal function was accompanied by reduction in NPHS1 gene expression (p<0.05). Moreover, we observed increase in PKM2, HK2 and IL-6 expression (p<0.05). FACS analysis revealed increase in relative and absolute numbers of CD146+NG2+ cells (p<0.05), as well as an increase of type 1 pericytes (NG2+Nestin-), when compared to non-DKD mice (p<0.05). Furthermore, the analysis showed that pericytes from DKD context had increase LAP-1 and IL-6 MFI, and less Nestin MFI (p<0.05).

Conclusion

Type 1 pericytes seems to contribute to DKD progression, through IL-6 secretion and TGF-b conversion from LAP-1. However, it is still necessary to evaluate the metabolic profile of pericyte during the DKD progression and how this cells communicate with other renal cells. FAPESP (2019/ 19/21359-3 and 2017/05264-7), CAPES and CNPq.

Funding

  • Government Support – Non-U.S.