ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on Twitter

Kidney Week

Abstract: TH-PO923

Myostatin Promotes Tubular Inflammation in Diabetic Nephropathy

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical


  • Verzola, Daniela, University of Genoa Di.M.I. Nephrology, Genoa, Italy
  • Carta, Annalisa, University of Genoa IRCCS San Martino, Abbasanta, Italy
  • Milanesi, Samantha, University of Genoa IRCCS San Martino, Abbasanta, Italy
  • Saio, Michela, University of Genoa, Hospital IRCCS-IST San Martino, Genova, Italy
  • Viazzi, Francesca, University of Genoa IRCCS AOU San Martino, Genova, Italy
  • Picciotto, Daniela, University of Genoa IRCCS AOU San Martino, Genova, Italy
  • Costigliolo, Francesca, University of Genoa IRCCS AOU San Martino, Genova, Italy
  • Barisione, Chiara, University of Genova, Genova, Italy
  • Garibotto, Giacomo, University of Genoa IRCCS AOU San Martino, Genova, Italy

Inflammation contributes to the tubulointerstitial lesions of diabetic nephropathy. Myostatin (MSTN), a member of the Transforming growth factor-β family, has been identified as a mediator of inflammation and insulin resistance in type 2 diabetes. MSTN has also been identified in the tubulointerstitium of porcine kidney, but its role in the human kidney is not known. The aims of the current study were (1) to investigate MSTN expression in the normal kidney and in kidney biopsies with documented diabetic nephropathy (DN); (2) to the functional role of MSTN in tubular inflammation and fibrosis, using an established PTEC culture system.


MSTN mRNA was analyzed in microdissected tubuli and glomeruli from normal kidneys (N=19), DN (n=23, proteinuria 3.8±1.0 g/d, eGFR= 33±7 ml/min) and IgA biopsies (n= 12, proteinuria 2.7 g/d, eGFR= 39±5 ml/min ) and protein was studied by immunohistochemistry. In vitro, HK-2 (human PTEC line) was exposed to MSTN (500 ng/ml) for 48 hours. We evaluated mRNAs by rt PCR, proteins by western blot, cell proliferation by CFSE incorporation, oxidative stress by CellROX staining.


Laser capture microdissection showed an overexpression of MSTN mRNA (~8- to 10-fold increase) in the tubulointerstitium compartment in DN. Immunoreactive MSTN was overexpressed in the tubulointerstitium from DN patients (~4-8 fold increase) but not in nondiabetic control subjects and co-localized with interstitial infiltrating CD45+ cells. The intensity of tubulointerstitial MSTN expression correlated directly with tubular atrophy ( R= 0.64; p<0.001). When proximal tubule HK-2 cells were treated with MSTN, they showed a decrease in proliferation, together with NF-kB activation and upregulation of downward inflammatory chemokines, SMAD 2/3 and fibronectin mRNA and protein. In addition, MSTN induced intracellular ROS release and upregulated NADPH oxidase, an effect which was mediated by ERK activation.


In conclusion, our data show that MSTN is upregulated in the tubulointerstitium of DN and associates with tubulointerstitial fibrosis. Its proinflammatory and profibrotic effects in human tubular cells suggests that MSTN plays a role in the progression of DN.


  • Government Support - Non-U.S.