NMN: A Promising Ally Against Kidney Fibrosis Linked to DNA Damage

Kidneys, our natural blood purification system, are susceptible to various forms of damage. A significant form of kidney damage is attributed to exposure to harmful chemicals or decreased blood flow. This is a common occurrence in hospital settings, affecting approximately 25-45% of patients in trauma or intensive care units. Unfortunately, there are no current therapeutic measures to accelerate kidney tissue repair or prevent subsequent scarring, medically termed as fibrosis. Consequently, there's an urgent need to understand the progression of fibrosis following kidney injuries to develop novel therapeutic strategies.

NMN as a Potential Therapeutic Strategy

A research team led by Yang from Peking University First Hospital in Beijing, China, released a study in Frontiers in Physiology pinpointing nicotinamide mononucleotide (NMN) as a possible solution for reducing kidney tissue scarring after damage. Their findings suggest that NMN prevents kidney cell damage, aging, and inflammation, thereby helping in the prevention and treatment of tissue fibrosis. This investigation into NMN's therapeutic value was prompted by previous studies demonstrating its effectiveness in DNA damage repair and scarring prevention in different organs. The research implies that NMN could be an efficient strategy for averting and treating kidney fibrosis post-injury.

Understanding NMN's Role as a NAD+ Precursor

NMN serves as a precursor molecule to nicotinamide adenine dinucleotide (NAD+), a metabolite found in every living cell. NAD+ plays an essential role in fundamental biological functions, such as DNA repair and energy metabolism, both crucial for cell function and tissue health. Given the high metabolic activity of kidney cells, they are incredibly susceptible to NAD+ depletion and subsequent ATP production impairment.

Restoring NAD+ levels using precursors like NMN has shown positive effects against fibrosis and age-related diseases. Therefore, NMN's potential to protect against DNA damage and metabolic dysfunction may prove beneficial in mitigating kidney fibrosis.

NMN's Impact on Kidney Cells Under Stress

To investigate NMN's impact on kidney fibrosis, Yang's team conducted experiments on cultured kidney cells. They induced kidney cell damage through chemical (hydrogen peroxide) and oxygen deprivation (ischemia), subsequently treating these cells with NMN (1 mM). Their findings revealed that NMN enhances cell survival and decreases the number of aged, non-proliferating cells. Furthermore, NMN effectively slowed the DNA damage processes in these damaged cells, reducing DNA-damaged cells from 32% to 22.6%. These outcomes strongly suggest that NMN can inhibit cellular programs leading to tissue scarring processes, at least in kidney cells.

The team also conducted experiments in mice to determine if NMN's protective effects in cultured cells would translate to live animals. They observed that NMN treatment significantly reduced the progression of DNA damage, suggesting it can impede the onset of tissue fibrosis. NMN treatment also restored kidney tissue scarring and reduced cell death in mice.

Final Thoughts on NMN and Kidney Tissue Scarring

"Our results collectively imply the DNA damage inhibition, antiaging and anti-inflammatory effects of NMN in kidneys, suggesting that NMN administration might be a promising strategy for preventing or treating kidney fibrosis after acute kidney injury," stated Yang's team.

Future exploration of NMN's role in injury-induced tissue scarring will necessitate clinical trials to determine if these findings can be reproduced in human subjects.

References

Jia Y, Kang X, Tan L, Ren Y, Qu L, Tang J, Liu G, Wang S, Xiong Z and Yang L (2021). Nicotinamide Mononucleotide Attenuates Renal Interstitial Fibrosis After AKI by Suppressing Tubular DNA Damage and Senescence. Front. Physiol. 12:649547. doi: 10.3389/fphys.2021.649547