Oral Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2017

Differences in matrix synthetic and degradative pathways may contribute to differences in susceptibility to development of renal changes in BALB/c and C57BL/6 mice. (#40)

Anh Tao 1 , Surya Sutanto 1 , Linda Ban 1 , Danqing Min 1 2 , Stephen Twigg 1 2 , Susan McLennan 1 2 3
  1. Greg Brown Diabetes and Endocrinology Research Laboratories, Sydney Medical School, Charles Perkins Centre and Bosch Institute, University of Sydney , Sydney, NSW, Australia
  2. Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
  3. NSW Health Pathology, Sydney, NSW, Australia

The BALB/c mouse is more prone to development of diabetic nephropathy (DN) than the C57BL/6. Furthermore, the relationship between matrix synthetic and degradative pathways in association with the development of DN in these strains has not been investigated.  

Diabetes (DM) was induced in 6-week-old male BALB/c and C57BL/6 mice (STZ: 3x65mg/kg), age-matched non-diabetic mice acted as control. Animals were euthanased 5, 10 and 30wks later. Kidneys were harvested for measurement of markers of inflammation (CXCL10 and MCP-1), profibrotic markers (TGFβ1 and CTGF), and matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) by qRT-PCR. Endogenous kidney MMP activity was measured using a fluorogenic substrate. Renal changes were assessed by histology.

In all DM animals blood glucose level was increased (P<0.01). In BALB/c mice renal changes were evident at 5wks of DM, with increased glomerular size, thickened basement membrane and mesangium expansion prominent by 30wks. In BALB/c, diabetes increased CXCL10 and MCP-1 (5-30wks) and TGFβ1 but not CTGF at 5 and 10wks (all P<0.01). MMPs (MMP-2, -14) and TIMPs -1 and -2 were increased at 5wks of DM (P<0.05), and at 10wks for MMP-14 and TIMP-2 (P<0.01). Kidney MMP activity was also increased at 10wks (P<0.05). The pattern for CXCL10 in C57BL/6, was similar, but MCP-1 was increased only at 5wks and TGFβ1 and CTGF were increased at all time points (P<0.05). In C57BL/6, the MMP profile was different with increased MMP-3 and- 9 at 5 and 10wks as well as increased TIMPs (P<0.05). Interestingly, in BALB/c animals, the mRNA levels of MMPs and TIMPs were all decreased at 30 weeks (P<0.05) but in C57BL/6 mice the increased TIMP-1 persisted (P<0.05).

This study suggests that there are subtle differences in response to diabetes in BALB/c and C57BL/6 mice which may contribute to the different susceptibility to the development of DN.