Pericytes, mural cells of the kidney peritubular capillaries, have been neglected until recently, and their function in kidney development, homeostasis, pathology and regeneration is only starting to be fully appreciated. In other organs, and also in cancer growth, the crucial role of pericytes in angiogenesis, vessel stabilization and capillary barrier functions is now established. Pericytes provide key molecular signals to endothelium for endothelial migration, growth and stabilization as new vessels. Recent studies from our lab have identified pericytes of the kidney peritubular capillaries as the major myofibroblast precursor, and therefore the cell responsible for fibrogenesis. Kidney injuries lead to pericyte detachment and migration away from peritubular capillaries as cells we call myofibroblasts. New evidence indicates that peritubular capillaries, which have lost pericytes due to this process, are unstable, have impaired barrier function and regress, leading to capillary rarefaction. Therefore capillary rarefaction, which results in organ ischemia, is intrinsically linked fibrogenesis. However pericyte detachment and migration are not necessarily permanent and prevention of detachment or promotion of reattachment may be central to normal organ regeneration. New studies have identified pericyte to endothelial signaling via Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) as a central pathway in regulating pericyte detachment and kidney disease progression. Directly following on from ARRA Challenge Grant funded work and working with a central hypothesis that failure to regenerate peritubular capillaries after injury may lead to interstitial fibrosis and chronic kidney injury wewill undertake the following studies.
Aim 1 : Using novel genetic ablative methods, determine the function of kidney pericytes in homoeostasis and injury responses in mouse kidney Aim 2. Determine the role of pericyte-derived TIMP3 and ADAMTS1 in regulation of microvascular stability and VEGF receptor signaling Aim 3. Define pericyte-derived VEGFA as a determinant of spontaneous &induced kidney disease progression.

Public Health Relevance

Acute Kidney Injury, Chronic Kidney Disease and End Stage Kidney Disease are major health burdens. Pericytes are cells of the kidney that have recently been descibed to play a major role in kidney disease. In health these cells nurture small blood vessels of the kidney but after injury migrate from the small vessels leading to instability and loss of these precious vessels. These studies will investigate the mechanisms by which pericytes nurture kidney blood vessels and the mechanisms by which they detach in response to injury and thereafter fail to nurture. In understanding these processes we hope to develop new therapies to treat kidney diseases.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
Project #
Application #
Study Section
Pathobiology of Kidney Disease Study Section (PBKD)
Program Officer
Hoshizaki, Deborah K
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Washington
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Ieronimakis, Nicholas; Hays, Aislinn; Prasad, Amalthiya et al. (2016) PDGFRα signalling promotes fibrogenic responses in collagen-producing cells in Duchenne muscular dystrophy. J Pathol 240:410-424
Lichtnekert, Julia; Kaverina, Natalya V; Eng, Diana G et al. (2016) Renin-Angiotensin-Aldosterone System Inhibition Increases Podocyte Derivation from Cells of Renin Lineage. J Am Soc Nephrol 27:3611-3627
Gomez, Ivan G; Roach, Allie M; Nakagawa, Naoki et al. (2016) TWEAK-Fn14 Signaling Activates Myofibroblasts to Drive Progression of Fibrotic Kidney Disease. J Am Soc Nephrol 27:3639-3652
Stefanska, Ania; Eng, Diana; Kaverina, Natalya et al. (2016) Cells of renin lineage express hypoxia inducible factor 2α following experimental ureteral obstruction. BMC Nephrol 17:5
Nakagawa, Naoki; Barron, Luke; Gomez, Ivan G et al. (2016) Pentraxin-2 suppresses c-Jun/AP-1 signaling to inhibit progressive fibrotic disease. JCI Insight 1:e87446
Stefanska, Ania; Eng, Diana; Kaverina, Natalya et al. (2015) Interstitial pericytes decrease in aged mouse kidneys. Aging (Albany NY) 7:370-82
Grazioli, Serge; Gil, Sucheol; An, Dowon et al. (2015) CYR61 (CCN1) overexpression induces lung injury in mice. Am J Physiol Lung Cell Mol Physiol 308:L759-65
Nakagawa, Naoki; Xin, Cuiyan; Roach, Allie M et al. (2015) Dicer1 activity in the stromal compartment regulates nephron differentiation and vascular patterning during mammalian kidney organogenesis. Kidney Int 87:1125-40
Kawakami, Takahisa; Gomez, Ivan G; Ren, Shuyu et al. (2015) Deficient Autophagy Results in Mitochondrial Dysfunction and FSGS. J Am Soc Nephrol 26:1040-52
Pamir, Nathalie; Liu, Ning-Chun; Irwin, Angela et al. (2015) Granulocyte/Macrophage Colony-stimulating Factor-dependent Dendritic Cells Restrain Lean Adipose Tissue Expansion. J Biol Chem 290:14656-67

Showing the most recent 10 out of 37 publications