Mitochondria-Targeted Peptide SS31 Attenuates Renal Tubulointerstitial Injury via Inhibiting Mitochondrial Fission in Diabetic Mice.

Yang SK, Li AM, Han YC, Peng CH, Song N, Yang M, Zhan M, Zeng LF, Song PA, Zhang W, Tang SQ, Zhang H

Oxidative medicine and cellular longevity2 Jun 2019Cited by 39 (Europe PMC)

PMID31281569PMCIDPMC6589270DOI10.1155/2019/2346580PepBankPUB-31281569

Summary

ObjectiveRenal tubular injury is an early characteristic of diabetic nephropathy (DN) that is related to mitochondrial dysfunction. In this study, we explore the effects and mechanisms of mitochondria-targeted peptide SS31 on renal tubulointerstitial injury in DN.Method40 C57BL/6 mice were randomly divided into control group, STZ group, STZ+SS31 group, and STZ+normal saline group. SS31 was intraperitoneally injected to the mice every other day for 24 weeks. Renal lesions and the expression of Drp1, Mfn1, Bcl-2, Bax, Caspase1, IL-1β, and FN were detected. In in vitro studies, HK-2 cells were incubated with different concentrations of D-glucose (5, 30 mM) or combined with SS31 and Drp1 inhibitor Midivi1. Mitochondrial ROS, membrane potential, and morphology have been detected to evaluate the mitochondrial function.ResultsCompared with diabetic mice, the levels of serum creatinine and microalbuminuria were significantly decreased in the SS31 group. Renal tubulointerstitial fibrosis, oxidative stress, and apoptosis were observed in diabetic mice, while the pathological changes were reduced in the SS31-treatment group. SS31 could decrease the expression of Drp1, Bax, Caspase1, IL-1β, and FN in the renal tissue of diabetic mice, while increasing the expression of Mfn1. Additionally, mitochondria exhibit focal enlargement and crista swelling in renal tubular cells of diabetic mice, while SS31 treatment could partially block these changes. An in vitro study showed that pretreatment with SS31 or Drp1 inhibitor Mdivi1 could restore the level of mitochondrial ROS, the membrane potential levels, and the expressions of Drp1, Bax, Caspase1, IL-1β, and FN in HK-2 cells under high-glucose conditions.ConclusionSS31 protected renal tubulointerstitial injury in diabetic mice through a decrease in mitochondrial fragmentation via suppressing the expression of Drp1 and increasing the expression of Mfn1.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study19

19 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
In diabetic mice, SS31 lowered serum creatinine compared with untreated diabetic mice.
In plain wordsIn diabetic mice, SS31 lowered serum creatinine more than in diabetic mice without SS31.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseSerum creatinine
Study
mousen: not reported in source
STZ-induced diabetic mice
Comparator
Diabetic mice
Outcome group
Kidney function · Kidney and urinary
Studied dose
Dose not stated · intraperitoneal · 24 weeksAs given in this study (mouse).
Source sentences
Summary
Compared with diabetic mice, the levels of serum creatinine and microalbuminuria were significantly decreased in the SS31 group.
1 context sentence(design, population, supporting numbers)
Summary · context
40 C57BL/6 mice were randomly divided into control group, STZ group, STZ+SS31 group, and STZ+normal saline group. SS31 was intraperitoneally injected to the mice every other day for 24 weeks.
Show in the study text Report a problemFND-3128156901
02AnimalAnimal study (in vivo)Efficacy outcome
In diabetic mice, SS31 lowered microalbuminuria compared with untreated diabetic mice.
In plain wordsIn diabetic mice, SS31 lowered urine albumin more than in diabetic mice without SS31.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseMicroalbuminuria
Study
mousen: not reported in source
STZ-induced diabetic mice
Comparator
Diabetic mice
Outcome group
Kidney function · Kidney and urinary
Studied dose
Dose not stated · intraperitoneal · 24 weeksAs given in this study (mouse).
Source sentences
Summary
Compared with diabetic mice, the levels of serum creatinine and microalbuminuria were significantly decreased in the SS31 group.
1 context sentence(design, population, supporting numbers)
Summary · context
40 C57BL/6 mice were randomly divided into control group, STZ group, STZ+SS31 group, and STZ+normal saline group. SS31 was intraperitoneally injected to the mice every other day for 24 weeks.
Show in the study text Report a problemFND-3128156902
03AnimalAnimal study (in vivo)Efficacy outcome
In diabetic mice, SS31 treatment reduced renal tubulointerstitial fibrosis.
In plain wordsIn diabetic mice, SS31 treatment reduced scarring in the kidney.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseRenal tubulointerstitial fibrosis
Study
mousen: not reported in source
STZ-induced diabetic mice
Outcome group
Kidney function · Kidney and urinary
Studied dose
Dose not stated · intraperitoneal · 24 weeksAs given in this study (mouse).
Source sentences
Summary
Renal tubulointerstitial fibrosis, oxidative stress, and apoptosis were observed in diabetic mice, while the pathological changes were reduced in the SS31-treatment group.
1 context sentence(design, population, supporting numbers)
Summary · context
40 C57BL/6 mice were randomly divided into control group, STZ group, STZ+SS31 group, and STZ+normal saline group. SS31 was intraperitoneally injected to the mice every other day for 24 weeks.
Show in the study text Report a problemFND-3128156903
04AnimalAnimal study (in vivo)Efficacy outcome
In diabetic mice, SS31 treatment reduced renal oxidative stress.
In plain wordsIn diabetic mice, SS31 treatment reduced oxidative stress in the kidney.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseRenal oxidative stress
Study
mousen: not reported in source
STZ-induced diabetic mice
Outcome group
Kidney function · Kidney and urinary
Studied dose
Dose not stated · intraperitoneal · 24 weeksAs given in this study (mouse).
Source sentences
Summary
Renal tubulointerstitial fibrosis, oxidative stress, and apoptosis were observed in diabetic mice, while the pathological changes were reduced in the SS31-treatment group.
1 context sentence(design, population, supporting numbers)
Summary · context
40 C57BL/6 mice were randomly divided into control group, STZ group, STZ+SS31 group, and STZ+normal saline group. SS31 was intraperitoneally injected to the mice every other day for 24 weeks.
Show in the study text Report a problemFND-3128156904
05AnimalAnimal study (in vivo)Efficacy outcome
In diabetic mice, SS31 treatment reduced renal apoptosis.
In plain wordsIn diabetic mice, SS31 treatment reduced cell death in the kidney.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseRenal apoptosis
Study
mousen: not reported in source
STZ-induced diabetic mice
Outcome group
Kidney function · Kidney and urinary
Studied dose
Dose not stated · intraperitoneal · 24 weeksAs given in this study (mouse).
Source sentences
Summary
Renal tubulointerstitial fibrosis, oxidative stress, and apoptosis were observed in diabetic mice, while the pathological changes were reduced in the SS31-treatment group.
1 context sentence(design, population, supporting numbers)
Summary · context
40 C57BL/6 mice were randomly divided into control group, STZ group, STZ+SS31 group, and STZ+normal saline group. SS31 was intraperitoneally injected to the mice every other day for 24 weeks.
Show in the study text Report a problemFND-3128156905
06AnimalAnimal study (in vivo)Mechanism
In diabetic mice, SS31 decreased Drp1 expression in renal tissue.
In plain wordsIn diabetic mice, SS31 lowered a mitochondrial fission protein (Drp1) in the kidney.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseRenal Drp1 expression
Study
mousen: not reported in source
STZ-induced diabetic mice
Outcome group
Mitochondrial function · Kidney and urinary
Studied dose
Dose not stated · intraperitoneal · 24 weeksAs given in this study (mouse).
Source sentences
Summary
SS31 could decrease the expression of Drp1, Bax, Caspase1, IL-1β, and FN in the renal tissue of diabetic mice, while increasing the expression of Mfn1.
1 context sentence(design, population, supporting numbers)
Summary · context
40 C57BL/6 mice were randomly divided into control group, STZ group, STZ+SS31 group, and STZ+normal saline group. SS31 was intraperitoneally injected to the mice every other day for 24 weeks.
Show in the study text Report a problemFND-3128156906
07AnimalAnimal study (in vivo)Mechanism
In diabetic mice, SS31 decreased Bax expression in renal tissue.
In plain wordsIn diabetic mice, SS31 lowered a cell-death protein (Bax) in the kidney.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseRenal Bax expression
Study
mousen: not reported in source
STZ-induced diabetic mice
Outcome group
Mitochondrial function · Kidney and urinary
Studied dose
Dose not stated · intraperitoneal · 24 weeksAs given in this study (mouse).
Source sentences
Summary
SS31 could decrease the expression of Drp1, Bax, Caspase1, IL-1β, and FN in the renal tissue of diabetic mice, while increasing the expression of Mfn1.
1 context sentence(design, population, supporting numbers)
Summary · context
40 C57BL/6 mice were randomly divided into control group, STZ group, STZ+SS31 group, and STZ+normal saline group. SS31 was intraperitoneally injected to the mice every other day for 24 weeks.
Show in the study text Report a problemFND-3128156907
08AnimalAnimal study (in vivo)Mechanism
In diabetic mice, SS31 decreased Caspase1 expression in renal tissue.
In plain wordsIn diabetic mice, SS31 lowered an inflammation-related enzyme (Caspase1) in the kidney.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseRenal Caspase1 expression
Study
mousen: not reported in source
STZ-induced diabetic mice
Outcome group
Inflammation markers · Kidney and urinary
Studied dose
Dose not stated · intraperitoneal · 24 weeksAs given in this study (mouse).
Source sentences
Summary
SS31 could decrease the expression of Drp1, Bax, Caspase1, IL-1β, and FN in the renal tissue of diabetic mice, while increasing the expression of Mfn1.
1 context sentence(design, population, supporting numbers)
Summary · context
40 C57BL/6 mice were randomly divided into control group, STZ group, STZ+SS31 group, and STZ+normal saline group. SS31 was intraperitoneally injected to the mice every other day for 24 weeks.
Show in the study text Report a problemFND-3128156908
09AnimalAnimal study (in vivo)Mechanism
In diabetic mice, SS31 decreased IL-1β expression in renal tissue.
In plain wordsIn diabetic mice, SS31 lowered an inflammation signal (IL-1β) in the kidney.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseRenal IL-1β expression
Study
mousen: not reported in source
STZ-induced diabetic mice
Outcome group
Inflammation markers · Kidney and urinary
Studied dose
Dose not stated · intraperitoneal · 24 weeksAs given in this study (mouse).
Source sentences
Summary
SS31 could decrease the expression of Drp1, Bax, Caspase1, IL-1β, and FN in the renal tissue of diabetic mice, while increasing the expression of Mfn1.
1 context sentence(design, population, supporting numbers)
Summary · context
40 C57BL/6 mice were randomly divided into control group, STZ group, STZ+SS31 group, and STZ+normal saline group. SS31 was intraperitoneally injected to the mice every other day for 24 weeks.
Show in the study text Report a problemFND-3128156909
10AnimalAnimal study (in vivo)Mechanism
In diabetic mice, SS31 decreased fibronectin expression in renal tissue.
In plain wordsIn diabetic mice, SS31 lowered a scarring protein (fibronectin) in the kidney.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseRenal fibronectin (FN) expression
Study
mousen: not reported in source
STZ-induced diabetic mice
Outcome group
Kidney function · Kidney and urinary
Studied dose
Dose not stated · intraperitoneal · 24 weeksAs given in this study (mouse).
Source sentences
Summary
SS31 could decrease the expression of Drp1, Bax, Caspase1, IL-1β, and FN in the renal tissue of diabetic mice, while increasing the expression of Mfn1.
1 context sentence(design, population, supporting numbers)
Summary · context
40 C57BL/6 mice were randomly divided into control group, STZ group, STZ+SS31 group, and STZ+normal saline group. SS31 was intraperitoneally injected to the mice every other day for 24 weeks.
Show in the study text Report a problemFND-3128156910
11AnimalAnimal study (in vivo)Mechanism
In diabetic mice, SS31 increased Mfn1 expression in renal tissue.
In plain wordsIn diabetic mice, SS31 raised a mitochondrial fusion protein (Mfn1) in the kidney.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseRenal Mfn1 expression
Study
mousen: not reported in source
STZ-induced diabetic mice
Outcome group
Mitochondrial function · Kidney and urinary
Studied dose
Dose not stated · intraperitoneal · 24 weeksAs given in this study (mouse).
Source sentences
Summary
SS31 could decrease the expression of Drp1, Bax, Caspase1, IL-1β, and FN in the renal tissue of diabetic mice, while increasing the expression of Mfn1.
1 context sentence(design, population, supporting numbers)
Summary · context
40 C57BL/6 mice were randomly divided into control group, STZ group, STZ+SS31 group, and STZ+normal saline group. SS31 was intraperitoneally injected to the mice every other day for 24 weeks.
Show in the study text Report a problemFND-3128156911
12AnimalAnimal study (in vivo)Mechanism
In diabetic mice, SS31 partially blocked the mitochondrial focal enlargement and crista swelling in renal tubular cells.
In plain wordsIn diabetic mice, SS31 partly blocked mitochondrial damage in kidney tubule cells.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseMitochondrial structure in renal tubular cells
Study
mousen: not reported in source
STZ-induced diabetic mice
Outcome group
Mitochondrial function · Kidney and urinary
Studied dose
Dose not stated · intraperitoneal · 24 weeksAs given in this study (mouse).
Source sentences
Summary
Additionally, mitochondria exhibit focal enlargement and crista swelling in renal tubular cells of diabetic mice, while SS31 treatment could partially block these changes.
1 context sentence(design, population, supporting numbers)
Summary · context
40 C57BL/6 mice were randomly divided into control group, STZ group, STZ+SS31 group, and STZ+normal saline group. SS31 was intraperitoneally injected to the mice every other day for 24 weeks.
Show in the study text Report a problemFND-3128156912
13LabIn vitro (cells)Mechanism
In HK-2 cells under high glucose, SS31 pretreatment restored mitochondrial ROS levels.
In plain wordsIn kidney cells under high glucose, SS31 pretreatment brought mitochondrial reactive oxygen species back toward normal.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseMitochondrial ROS in HK-2 cells
Study
n: not reported in source
HK-2 cells in high glucose
Outcome group
Mitochondrial function · Kidney and urinary
Studied dose
Dose not stated
Source sentences
Summary
An in vitro study showed that pretreatment with SS31 or Drp1 inhibitor Mdivi1 could restore the level of mitochondrial ROS, the membrane potential levels, and the expressions of Drp1, Bax, Caspase1, IL-1β, and FN in HK-2 cells under high-glucose conditions.
1 context sentence(design, population, supporting numbers)
Summary · context
In in vitro studies, HK-2 cells were incubated with different concentrations of D-glucose (5, 30 mM) or combined with SS31 and Drp1 inhibitor Midivi1.
Show in the study text Report a problemFND-3128156913
14LabIn vitro (cells)Mechanism
In HK-2 cells under high glucose, SS31 pretreatment restored mitochondrial membrane potential.
In plain wordsIn kidney cells under high glucose, SS31 pretreatment brought mitochondrial membrane potential back toward normal.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseMitochondrial membrane potential in HK-2 cells
Study
n: not reported in source
HK-2 cells in high glucose
Outcome group
Mitochondrial function · Kidney and urinary
Studied dose
Dose not stated
Source sentences
Summary
An in vitro study showed that pretreatment with SS31 or Drp1 inhibitor Mdivi1 could restore the level of mitochondrial ROS, the membrane potential levels, and the expressions of Drp1, Bax, Caspase1, IL-1β, and FN in HK-2 cells under high-glucose conditions.
1 context sentence(design, population, supporting numbers)
Summary · context
In in vitro studies, HK-2 cells were incubated with different concentrations of D-glucose (5, 30 mM) or combined with SS31 and Drp1 inhibitor Midivi1.
Show in the study text Report a problemFND-3128156914
15LabIn vitro (cells)Mechanism
In HK-2 cells under high glucose, SS31 pretreatment restored Drp1 expression.
In plain wordsIn kidney cells under high glucose, SS31 pretreatment brought Drp1 back toward normal.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseDrp1 expression in HK-2 cells
Study
n: not reported in source
HK-2 cells in high glucose
Outcome group
Mitochondrial function · Kidney and urinary
Studied dose
Dose not stated
Source sentences
Summary
An in vitro study showed that pretreatment with SS31 or Drp1 inhibitor Mdivi1 could restore the level of mitochondrial ROS, the membrane potential levels, and the expressions of Drp1, Bax, Caspase1, IL-1β, and FN in HK-2 cells under high-glucose conditions.
1 context sentence(design, population, supporting numbers)
Summary · context
In in vitro studies, HK-2 cells were incubated with different concentrations of D-glucose (5, 30 mM) or combined with SS31 and Drp1 inhibitor Midivi1.
Show in the study text Report a problemFND-3128156915
16LabIn vitro (cells)Mechanism
In HK-2 cells under high glucose, SS31 pretreatment restored Bax expression.
In plain wordsIn kidney cells under high glucose, SS31 pretreatment brought Bax back toward normal.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseBax expression in HK-2 cells
Study
n: not reported in source
HK-2 cells in high glucose
Outcome group
Mitochondrial function · Kidney and urinary
Studied dose
Dose not stated
Source sentences
Summary
An in vitro study showed that pretreatment with SS31 or Drp1 inhibitor Mdivi1 could restore the level of mitochondrial ROS, the membrane potential levels, and the expressions of Drp1, Bax, Caspase1, IL-1β, and FN in HK-2 cells under high-glucose conditions.
1 context sentence(design, population, supporting numbers)
Summary · context
In in vitro studies, HK-2 cells were incubated with different concentrations of D-glucose (5, 30 mM) or combined with SS31 and Drp1 inhibitor Midivi1.
Show in the study text Report a problemFND-3128156916
17LabIn vitro (cells)Mechanism
In HK-2 cells under high glucose, SS31 pretreatment restored Caspase1 expression.
In plain wordsIn kidney cells under high glucose, SS31 pretreatment brought Caspase1 back toward normal.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseCaspase1 expression in HK-2 cells
Study
n: not reported in source
HK-2 cells in high glucose
Outcome group
Inflammation markers · Kidney and urinary
Studied dose
Dose not stated
Source sentences
Summary
An in vitro study showed that pretreatment with SS31 or Drp1 inhibitor Mdivi1 could restore the level of mitochondrial ROS, the membrane potential levels, and the expressions of Drp1, Bax, Caspase1, IL-1β, and FN in HK-2 cells under high-glucose conditions.
1 context sentence(design, population, supporting numbers)
Summary · context
In in vitro studies, HK-2 cells were incubated with different concentrations of D-glucose (5, 30 mM) or combined with SS31 and Drp1 inhibitor Midivi1.
Show in the study text Report a problemFND-3128156917
18LabIn vitro (cells)Mechanism
In HK-2 cells under high glucose, SS31 pretreatment restored IL-1β expression.
In plain wordsIn kidney cells under high glucose, SS31 pretreatment brought IL-1β back toward normal.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseIL-1β expression in HK-2 cells
Study
n: not reported in source
HK-2 cells in high glucose
Outcome group
Inflammation markers · Kidney and urinary
Studied dose
Dose not stated
Source sentences
Summary
An in vitro study showed that pretreatment with SS31 or Drp1 inhibitor Mdivi1 could restore the level of mitochondrial ROS, the membrane potential levels, and the expressions of Drp1, Bax, Caspase1, IL-1β, and FN in HK-2 cells under high-glucose conditions.
1 context sentence(design, population, supporting numbers)
Summary · context
In in vitro studies, HK-2 cells were incubated with different concentrations of D-glucose (5, 30 mM) or combined with SS31 and Drp1 inhibitor Midivi1.
Show in the study text Report a problemFND-3128156918
19LabIn vitro (cells)Mechanism
In HK-2 cells under high glucose, SS31 pretreatment restored fibronectin expression.
In plain wordsIn kidney cells under high glucose, SS31 pretreatment brought fibronectin back toward normal.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseFibronectin expression in HK-2 cells
Study
n: not reported in source
HK-2 cells in high glucose
Outcome group
Kidney function · Kidney and urinary
Studied dose
Dose not stated
Source sentences
Summary
An in vitro study showed that pretreatment with SS31 or Drp1 inhibitor Mdivi1 could restore the level of mitochondrial ROS, the membrane potential levels, and the expressions of Drp1, Bax, Caspase1, IL-1β, and FN in HK-2 cells under high-glucose conditions.
1 context sentence(design, population, supporting numbers)
Summary · context
In in vitro studies, HK-2 cells were incubated with different concentrations of D-glucose (5, 30 mM) or combined with SS31 and Drp1 inhibitor Midivi1.
Show in the study text Report a problemFND-3128156919

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Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
10 Oct 2026, 08:19 UTC
Study results updated
Version 1
9 Oct 2026, 02:47 UTC
First added · source update from Europe PMC

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