Adipose-derived stem cells exosomal KLF3-AS1 attenuates ovarian function by YBX1/PI3K/Akt/mTOR signaling

Wei Zhao1,2, Haili Zhang3, Liyan Zhang1

  • 11Department of Reproductive Center, Xilingol League Central Hospital, Inner Mongolia Xilingol League, 026000, China.

PubMed
Abstract

Insights

Adipose-derived stem cell exosomes carrying lncRNA KLF3-AS1 can rejuvenate aging ovaries by improving granulosa cell viability. This therapy targets YBX1 and the PI3K/AKT/mTOR pathway, offering a novel approach for ovarian aging.

Area of Science:

  • Reproductive Biology
  • Stem Cell Biology
  • Molecular Biology

Background:

  • Adipose-derived stem cell (ADSC)-derived exosomes are investigated for therapeutic delivery of bioactive molecules like long non-coding RNAs (lncRNAs).
  • Long non-coding RNAs (lncRNAs) are key regulators enriched in exosomes, influencing cellular functions.
  • This study focuses on the lncRNA KLF3-AS1 delivered by ADSC exosomes and its impact on ovarian aging.

Purpose of the Study:

  • To investigate the therapeutic potential of ADSC-derived exosomal KLF3-AS1 in mitigating ovarian aging.
  • To elucidate the underlying molecular mechanisms involving YBX1 and the PI3K/AKT/mTOR signaling pathway.

Main Methods:

  • ADSCs were isolated, and exosomes were characterized.
  • ADSC-derived exosomes were engineered to deliver KLF3-AS1 and administered to aged female mice.
  • Ovarian function, follicular development, and cell apoptosis/senescence were assessed.
  • Molecular interactions (RNA pulldown, RIP) and signaling pathway activation (PI3K/AKT/mTOR) were analyzed.

Main Results:

  • ADSC-derived exosomes successfully delivered KLF3-AS1 to primary granulosa cells (pGCs).
  • Exosomal KLF3-AS1 treatment improved ovarian weight, enhanced follicular development, and reduced apoptosis in aged mice.
  • KLF3-AS1 directly interacts with YBX1, modulating the PI3K/AKT/mTOR pathway.
  • KLF3-AS1 depletion reversed the beneficial effects, while YBX1 overexpression rescued them.

Conclusions:

  • ADSC-derived exosomal KLF3-AS1 demonstrates a therapeutic effect on ovarian aging.
  • The mechanism involves targeting YBX1 and activating the PI3K/AKT/mTOR signaling pathway.
  • This approach enhances pGC viability and improves ovarian function in aged individuals.

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...