Kidney fibrosis is the final common pathway of all chronic kidney diseases but there is no approved drug to treat kidney fibrosis in the United States. There is general agreement that myofibroblasts are the cell type responsible for scar formation in fibrotic kidney disease, and ablating these cells improves kidney function in experimental models. However, there is very little information regarding small molecules that might alter myofibroblast function and reduce scar. Here we propose to dissect the ability of retinoic acid and its precursors to ameliorate kidney fibrosis as a foundation for establishing a new treatment paradigm. Our preliminary data indicates that retinoids inhibit myofibroblast function, and we will validate this observation using complementary strategies in vitro and in vivo. The data generated will establish a clear path towards translation of a new therapy to prevent kidney fibrosis by targeting retinoic acid signaling in myofibroblasts.

Public Health Relevance

Kidney fibrosis is the leading cause of kidney failure worldwide, and represents an enormous health burden. We propose to understand how retinoic acid, a derivative of vitamin A, blocks kidney fibrosis in experimental models. We hypothesize that treatment with a retinoic acid precursor will block fibrosis, but without the toxic effects associated with giving patients retinoic acid itself. With this information, we will be in positionto validate retinoid-based treatment strategies to prevent kidney fibrosis from progressing to end stage kidney disease.

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
Brigham and Women's Hospital
United States
Zip Code
Kramann, Rafael; Machado, Flavia; Wu, Haojia et al. (2018) Parabiosis and single-cell RNA sequencing reveal a limited contribution of monocytes to myofibroblasts in kidney fibrosis. JCI Insight 3:
Ó hAinmhire, Eoghainín; Humphreys, Benjamin D (2017) Fibrotic Changes Mediating Acute Kidney Injury to Chronic Kidney Disease Transition. Nephron 137:264-267
Kramann, Rafael; Wongboonsin, Janewit; Chang-Panesso, Monica et al. (2017) Gli1+ Pericyte Loss Induces Capillary Rarefaction and Proximal Tubular Injury. J Am Soc Nephrol 28:776-784
Miyagi, Ayano; Lu, Aiwu; Humphreys, Benjamin D (2016) Gene Editing: Powerful New Tools for Nephrology Research and Therapy. J Am Soc Nephrol 27:2940-2947
Ó hAinmhire, Eoghainín; Humphreys, Benjamin D (2016) A Plumbing Solution for Stem Cell-Derived Kidneys. Transplantation 100:3-4
Kramann, Rafael; Goettsch, Claudia; Wongboonsin, Janewit et al. (2016) Adventitial MSC-like Cells Are Progenitors of Vascular Smooth Muscle Cells and Drive Vascular Calcification in Chronic Kidney Disease. Cell Stem Cell 19:628-642
Maarouf, Omar H; Aravamudhan, Anusha; Rangarajan, Deepika et al. (2016) Paracrine Wnt1 Drives Interstitial Fibrosis without Inflammation by Tubulointerstitial Cross-Talk. J Am Soc Nephrol 27:781-90
Chang-Panesso, Monica; Humphreys, Benjamin D (2015) CD248/Endosialin: A Novel Pericyte Target in Renal Fibrosis. Nephron 131:262-4
Kramann, Rafael; Kusaba, Tetsuro; Humphreys, Benjamin D (2015) Who regenerates the kidney tubule? Nephrol Dial Transplant 30:903-10
Kramann, Rafael; Schneider, Rebekka K; DiRocco, Derek P et al. (2015) Perivascular Gli1+ progenitors are key contributors to injury-induced organ fibrosis. Cell Stem Cell 16:51-66

Showing the most recent 10 out of 12 publications